Speciality
Spotlight

 




 


Endocrinology


   

  




Diabetes

        

  • Mayer-Davis
    EJ, for the IRAS Investigators [Univ of South Carolina, Columbia: Wake Forest Univ. Winston-Salem, NC; Permanente Med Group Inc, Oakland, calif; et al]


    Intensity and Amount of Physical Activity in Relation to Insulin Sensitivity: The Insulin Resistance Atherosclerosis Study


    JAMA 279: 669-674, 1998

          

    After an intravenous glucose tolerance test insulin sensitivity was used to compare the exercising and non-exercising groups.

       

  • Michael
    F Greene, Massachusetts General Hospital Boston.


    Oral
    Hypoglycemic Drugs for Gestational Diabetes

    N
    Engl J Med 2000; 343(16), 19 October 2000, pg. 1178

       

    Early
    experience with first-generation sulfonylurea drugs
    such as tolbutamide and chlorpropamide included
    numerous cases of profound and prolonged
    hyperinsulinemic hypoglycemia among neonates.

       

    In
    studies in vitro, the authors demonstrated that
    glyburide did not cross the human placenta to any
    appreciable extent, but the same was not true for
    other sulfonylurea drugs. The concern about the transplacental effects of other sulfonylurea
    drugs therefore remains.

          

  • Oded
    Langer, Deborah L Conway, Michael D Berkus, Elly
    M.-J. Xenakis and Olga Gonzales.


    A
    Comparison of Glyburide and Insulin in Women with
    Gestational Diabetes Mellitus.

    N
    Engl J Med 2000; 343:1134-8.

      

    Women
    with gestational diabetes (diabetes in pregnant
    women) are not treated with sulphonylurea drugs
    because of concern about teratogenicity and neonatal
    hypoglycaemia. Sulphonylurea drugs cross the placental barrier.
    As a result there is a chance of
    teratogenicity. Also
    the hypoglycaemic action in the new born is quite
    severe and may produce hypoglycaemic ill-effects in
    the newborn. The new sulphonylurea called glyburide
    does not cross the placental barrier.

       

    The
    adverse reactions in the newborn are therefore
    avoided and control of diabetes in the mother is as
    good as with insulin. Both in terms of efficacy and
    adverse reactions there is no statistical
    significant difference.

        

  • R
    Turner, for the UK Prospective Diabetes 
    Study Group (Radcliffe Infirmary, Oxford,
    England)


    Tight
    Blood Pressure Control and Risk of Macrovascular and
    Microvascular Complications in Type 2 Diabetes:
    UKPDS 38.

    Bmj
    317: 703-713, 1998.

        

    Editors
    comment
    :
    It is possible that the benefit of treatment with
    ACE inhibitors of diabetic nephropathy is more due
    to tight control of blood pressure which is
    achieved by addition of ACE inhibitors than
    the ACE inhibitors itself.

        

  • Osei
    Kwame – Diabetes

    YB of Endocrinology, 2000, p.339

        


    Introduction :

    Diabetes mellitus has become a global epidemic. It is projected that by 2025 diabetes will afflict 300 million people worldwide. The driving force for this global epidemic is an increasingly sedentary lifestyle and, consequently, obesity. The introduction of a new classification, with fasting plasma glucose used as a diagnostic tool (with lower fasting glucose levels of 126 mg/dL), was geared toward increasing the rates of early diagnosis. It has the potential of preventing long-term complication of the disease and its attendant morbidity and mortality.

        


    It has been demonstrated that tight glycemic control is beneficial in patients with both type 1 and type 2 diabetes. During the past 25 years, morbidity associated with cardiovascular diseases continued to decline in non-diabetic populations; those with diabetes, especially females, continued to experience increasing morbidity and mortality from cardiovascular diseases. This calls for new emphasis on aggressive triple therapy for patients with diabetes: normalize glucose, blood pressure, and atherogenic profile.

       

  • Pittet
    D, Wyssa B, Herter-Clavel C, et al [Univ Hosp of
    Geneva, Switzerland]

    Outcome of
    Diabetic Foot Infections Treated Conservatively : A
    Retrospective Cohort Study with Long-term Follow-up


    Arch
    Intern Med 159: 851-856, 1999

        

    Diabetic
    foot lesions are the cause of more hospitalizations
    than any other complications of diabetes. Effective
    guidance needs to be enunciated to minimize human
    and financial cost of diabetic foot lesions. A
    5-year retrospective cohort study with prospective
    long-term follow up was undertaken to identify
    criteria predictive of failure of conservative
    treatment of such lesions.

        

    The Wagner classification system was used for this
    study. Variables examined included patient
    demographics, infection and diabetes.

        

    Of 120 patients, 74% had contiguous osteomyelitis,
    deep tissue involvement or gangrene. 13% underwent
    immediate amputation. 
    Of the remaining, conservative treatment was
    successful in 63% of cases. 21 of 26 [81%] with skin
    ulcers. 35 of 50 [70%] with deep tissue infection or
    suspected osteomyelitis and 1 of 15 [7%] with
    gangrene.

       

    Independent factors predictive of failure were
    fever, elevated creatinine, prior hospitalization
    for diabetic foot lesion, duration of diabetes.

       

    Conservative
    measures including prolonged culture guided
    parenteral or oral antibiotics was successful
    without amputation in 63% of diabetic foot lesion.

         

  • Hoffman J, Spengler M [Clinical Research Collaborative Study Group,
    Essen, Germany: Bayer AG, Leverkusen, Germany

    Efficacy of 24-Week Monotherapy With Acarbose, Metformin, or Placebo in Dietary-treated NIDDM patients – The Essen -II Study

    Am J Med 103: 483-490, 1997

       


    This is the first article to compare the efficacy of acarbose and metformin in the treatment of
    NIDDM, with placebo control. All the subjects of study were on a diet control regime only between the ages of 37 and 70 years. 

       


    Dose of acarbose was 100 mgm tablet thrice a day orally with food; metformin was given as 850 mgm tablet twice a day.

       


    Acarbose in addition to reducing blood glucose levels also reduced cholesterol levels, whereas metformin acts only on the former. Lactic acidosis reported with metformin seems not to occur with
    acarbose.

       

  • Diabetes
    Mellitus-Miscellaneous


    Levetan CS, Passaro M, Jablonski K, et al [Medlantic Research Inst, Washington, DC; Washington Hosp
    Ctr, Washington, DC]


    Unrecognized Diabetes among Hospitalized Patients


    Diabetes Care 21: 246-249, 1998

       


    Missing diabetes in patients admitted for other disorders is not uncommon. Glucose levels in the range around 200
    mg/dL is often ascribed to infections or stress. Early detection of disease may lead to prevention of subsequent complications, hence all such hyperglycemias need to be investigated.

       
        

  • Andrew J Krentz, Clifford J Bailey et al

    Thiazolidinediones for type 2 diabetes

    New agents reduce insulin resistance but need long term clinical trials

    BMJ, Vol.321, July 29, 2000, pg. 252-253

      

    Insulin resistance (reduced action of insulin) is a prominent defect in type 2 diabetes. Before the introduction of troglitazone in 1997 metformin was the only drug able to sensitize target tissues to insulin. Troglitazone is superseded by more potent agents, rosiglitazone and pioglitazone. 



    Patients with insulin resistance have elevated serum TG and low HDL. This dyslipidemia contributes to risk of atherosclerotic cardiovascular disease. Thiazolidonediones increase HDL and rosiglitazone protects against endothelial dysfunction, lowers BP in insulin resistant and hypertensive rats.



    Clinical trials show that combination therapy using a thiazolidinedione with metformin (main action of which is to reduce glucose production by liver) or a sulphonylurea is particularly effective in lowering glucose concentrations.



    Extensive use of rosiglitazone and pioglitazone has produced little evidence that it has caused hepatic impairment. They are contraindicated in patients with liver damage. Cardiac failure is a contraindication and patients with reduced cardiac reserve need close monitoring. Pioglitazone induces cytochrome P450 (isoform CYP3A4) and the possibility of drug interactions e.g. with oral contraceptives.

      

  • Irene M Stratton, Amanda I Adler, et al 

    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.

    BMJ, Vol.321, Aug.12, 2000, pg.405-412.

      

    The objective of the study was to determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complication in patients with type 2 diabetes. It was carried out in 4585 Asian Indian, white and Afro-Caribbean UKPDS (UK prospective diabetes study) patients. Incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbAtc was associated with reductions of risk of 21% for any end-point related to diabetes. The lowest risk being in those with HbAtc values in the normal range (<60%).

       

  • Editorial – Jaakko Tuomilehto

    Controlling glucose and blood pressure in type 2 diabetes. 

    Starting treatment earlier may reduce complications.

    BMJ. Vol.321, Aug.12, 2000, pg.394-395.

      

    The main questions have been when should we start treatment, what is the target level during treatment and what is the best method of treatment, since there are no obvious cut-off points for B.P. or glucose or cholesterol concentrations that would guide clinical decisions.



    Comparisons with observational data have shown that antihypertensive drugs reduce the risk of stroke as predicted, but the reduction in the risk of myocardial infarction is less than expected. Treatment of hypercholesterolaemia with statins reduces the risk of myocardial infarction as predicted, whereas the effect on the risk of stroke seems larger than expected.

      

    The results of UKPDS studies reveal that patients with type 2 diabetes whose hypertension is tightly controlled reduce their risk of macrovascular complications to a greater extent than estimated. The data clearly show that there are no natural thresholds under which the risk of microvascular and macrovascular complications in diabetes are fully prevented but the risk increases steadily with rising levels of risk factors. The lower the level of blood glucose, HbAtcc, or BP, the lower the risk of complications.



    It is difficult to maintain reductions in glucose concentrations and BP even when using multiple drugs that in short term trials have produced excellent results. This was also confirmed in the UKPDS. Thus, the alternative possibility would be to start treatment at lower levels than those currently used as thresholds.



    A large European epidemiological study showed that postprandial glucose concentration is a better predictor of mortality than is fasting glucose. Perhaps impaired glucose tolerance should be an indication for treatment. There is a need to carry out controlled clinical trials to find out whether lowering glucose concentrations at the levels of impaired glucose tolerance will reduce microvascular and macrovascular complications

      

  • A M James Shapiro, Jonathan R.T.Lakey et al 

    Islet transplantation in seven patients with type I diabetes mellitus using a glucocorticoid – free immunosuppressive regimen.

    New Eng J Med. Vol.343, July 27, 2000, pg.230

       

    Seven consecutive patients with type I diabetes and a history of severe hypoglycaemia and metabolic instability underwent islet transplantation in conjunction with a gluco corticoid free immuno suppressive regimen consisting of sirolimus, tacrolimus and daclizumab. Islets were isolated by ductal perfusion with cold purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolisation.



    Authors’ observations were that in patients with type I diabetes, islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid free immunosuppression is combined with the infusion of an adequate islet mass.

      

  • Editorial _ R Paul Robertson

    Successful islet transplantation for patients with diabetes – fact or fantasy ?

    New Eng J Med. Vol.343, July 27, 2000, pg.289-290.

      

    Shapiro and colleagues report 7 transplant recipients with type I diabetes who received an average of 800,000 islets maintained normoglycaemia and glycosylated haemoglobin values without exogenous insulin for an average of 1 year. The key to this impressive outcome include transplanting islets of very high quality as soon as possible after harvest from cadaveric donors and modifying conventional immunosuppressive regimen. Modifications involved eliminating glucocorticoids, using a low dose of tacrolimus and a conventional dose of sirolimus and adding daclizumab. Glucocorticoids and tacrolimus are known to affect beta cell function and survival adversely. It is possible that these 2 drugs and cyclosporine, which formed the usual regimen in prior trials, were the likely culprits leading to islet failure.



    Currently, transplantation of whole pancreas results in insulin independence and normalisation of glycosylated haemoglobin values for 3 years in 70-80% of patients. The less invasive procedure of islet transplantation should take precedence.

        

  •  Journal Scan

    Basic Research


    Heart 2001; 85:373-374




    The glitazones, which are effective anti-diabetic agents, may actually be
    antiatherogenic. By changing the biochemical pathway of peroxisome proliferator activated receptors
    (PPAR), the glitazones cause stimulation of a LDL scavenger receptor, SR-A. This may help in lowering the accumulation of lipids in macrophages.

        

  • General Cardiology

    Diabetic heart disease: clinical considerations


    Heart 2001; 85: 463.




    Coronary heart disease in diabetics is slightly different than in a non-diabetic because of autonomic neuropathy. Symptoms are comparatively mild. Atherosclerosis is more different and widespread in diabetes. However response to medical treatment is at least as good as in non-diabetes.

        


    From the surgical point of view, angioplasty and bypass is more difficult in diabetics because of the diffused nature of obstruction in the coronary arteries. However, bypass surgery is to be preferred to angioplasty. ACE inhibitors are of particular value in diabetics and coronary heart diseases, because this group of drugs minimises microvascular complications both in heart and the kidney.

         

  • Balkau
    B, Shipley M, Jarrett RJ, et al [INSERM,
    Villejuif, France; Univ of Kuopio, Finland; Univ
    College Med School, London; et al ]

    High Blood Glucose Concentration is a Risk
    Factor for Mortality in Middle-aged 

    Nondiabetic Men : 20-Year Follow-up in the
    Whitehall Study, the Paris Prospective Study,
    and the Helsinki Policemen Study



    Diabetes Care 21: 360-367, 1998


       

    High blood glucose levels not tantamount to a
    diagnosis of diabetes were evaluated as risk
    factors involved in causation of death due to
    all causes. Men between 44-55 years were given a
    standard 2 hour glucose tolerance test and
    followed up for 20 years. The total was made up
    of 10,025 in the Whitehall Study, 6629 in the
    Paris group and 631 in the Helsinki police men.
    Deaths from cardiovascular disease, coronary
    heart disease [CHD] and neoplasms were
    evaluated.

       

    Policemen had the maximum incidence in the all
    cause group except neoplasms. Deaths from
    cardiovascular and CHD were more than would be
    expected. Information of this type may suggest
    early control of glucose levels.

        
  • Landau
    Z [Kaplan Hosp, Rehovot Israel]

    Topical Hyperbaric Oxygen and Low Energy Laser
    for the Treatment of Diabetic Foot Ulcers

    Arch Orthop Trauma Surg 117: 156-158, 1998 


       

    50 diabetic subjects had nonhealing foot ulcers of 9
    months mean duration. 15 received topical hyperbaric
    oxygen alone and 35 in addition were given low
    energy laser. 25 treatments over a period of 3
    months resulted in curing 43 ulcerated feet.

        
  • Endocrine-Miscellaneous

    Bartalena L, Marcocci C, Bogazzi F, et al [Istituto
    di Endocrinologia, Pisa, Italy; Clinica Oculistica,
    Pisa, Italy; Univ of Pisa, Italy; et al]

    Relation Between therapy for Hyperthyroidism and
    the Course of Graves’ Ophthalmopathy

    N Engl J Med 338: 73-78, 1998


       

    443 patients of ‘Graves’ disease were treated with
    methimazole for 3 to 4 months. Radiotherapy [120 to
    150 (G ] for 18 months radioiodine and prednisone [
    0.4 to 0.5 mg/kg] for 3 months were given to some
    and methimazole was continued for others.

        

    Opthalmopathy began or became worse in 6 months of
    treatment with radioiodine alone. This was observed
    in 23 of the 150 subjects. Those who smoked
    outnumbered the non-smokers. 140 subjects treated
    with radioiodine and prednisone revealed either
    regression of ocular changes or non development of
    such changes if they had none at the onset. In the
    group of 148 on methimazole 3/74 with ocular changes
    improved, four developed them or became worse. 141
    maintained their status quo.

        

    This study is important as it emphasizes the role of
    autoimmunity in the pathogenisis of opthalmopathy in
    hyperthyroidism thus bringing out the role of a
    corticosteriod in both prevention and therapy of the
    evolved state

         

  • Hannele Yki-Jarvinen (Dept. of Medicine, Univ. of Helsinki, Helsinki, Finland)

    Management of Type 2 Diabetes Mellitus and Cardiovascular Risk

    Drugs Nov.2000; 60(5)p. 975-983

      

    Very often NIDDM (type 2 diabetes) is associated with hypertension. The disease carries increased risk of microvascular and macrovascular complications. It has now been shown that treatment of hyperglycemia is very effective in reducing microvascular disease but is not so effective in reducing macrovascular disease such as myocardial infarction, stroke and diabetic foot. The authors postulate that prevention of macrovascular disease is much more effectively treated by controlling hypertension, hypercholesterolaemia and small doses of aspirin.

        

  • Ian W Campbell, Victoria Hospitla, Kirkcaldy, Fife, Scotland 

    Antidiabetic Drugs Present and Future

    Will Improving Insulin Resistance Benefit Cardiovascular Risk in Type 2 Diabetes Mellitus?

    Drugs Nov.2000, 60(5), 1017-1028

      

    This survey in Scotland has revealed that treatment with sulfonylureas and insulin reduced only microvascular complication of diabetes but not the macrovascular complications. The only drugs, which possibly may be of benefit in reducing macrovascular complications are metformin and the glitazone group of insulin sensitizers. In addition, the statins would be of great use in the treatment of dyslipidaemia. Metformin particularly reduces glycosylated haemoglobin levels and reduces diabetes related risk and death by more than 36%. Metformin also reduces triglycerides and LDL cholesterol and slightly increases HDL. Pioglitazone also increases HDL cholesterol.

      

  • PG Tawalkar

    Editorial – The Diabetic Foot

    JAPI, Vol.49, May 2001, p. 509

        


    The diabetic foot is one of the commonest complications of diabetes. The major factors involved in the causation are ischemia, neuropathy and infection. Delayed wound healing, dyslipidemias and tobacco worsen the problems in addition to impaired sensation. The dry fissured skin is the portal of entry for microorganisms and can lead to osteomyelitis. Very vigorous antibiotic treatment is required for diabetic foot infections, and surgical incision and drainage are important. Needless to say that control of blood glucose is important but surgical procedures should start even before complete blood sugar
    control.

       

  • C J Ostgren, U Lindblad, J Ranstam, et al (Malmo Univ. Sweden; Odeshog Health Care Centre Sweden; Skaraborg Inst, Skovde, Sweden; et al)

    Associations Between Smoking and
    b-Cell Function in a Non-hypertensive and Non-diabetic Population: Skaraborg Hypertension and Diabetes Project.


    Diabetic Med 17: 445-450, 2000.

         


    Smoking increases the risk of type-2 diabetes, probably by inducing increased insulin resistance and also a direct adverse effect on pancreatic tissue. The effects of smoking on
    b-cell function, excluding the effects of hypertension and diabetes were studied among 874 patients.

         


    This community based analysis of subjects, suggests that smoking may adversely affect b-cell function, at least in men. Smoking also has been associated with increased microvascular disease especially retinopathy.

          

  • L Chaillous, for the Diabetes Insuline Orale Group (Universitaires de Nantes, France; et al)

    Oral insulin administration and residual b-cell function in Recent-Onset type-1 Diabetes: A Multicentre Randomized Controlled Trial.


    Lancet, 356, 545-549, 2000

         


    The study group of 131 auto antibody-positive patients with diabetes was enrolled within 2 weeks of diagnosis.

        


    Oral insulin (2.5mg or 7.5mg) or placebo was given at random to patients for one year, in addition to subcutaneous insulin therapy.

         


    Oral administration of insulin at the doses used in this trial and initiated at the clinical onset of type-1 diabetes did not prevent deterioration of ß-cell function in this group of patients. 

            

  • F. Shojaee-Moradie, A Schuttler et al (King’s College, London etc.)

    Novel Hepatoselective Insulin Analog: Studies with a Covalently Linked Thyroxyl-Insulin Complex in Humans.

    Diabetes Care 23: 1124-1129, 2000

         


    A thyroxyl-insulin analogue with restricted access to receptor sites in peripheral tissues was evaluated to determine whether it displayed relative hepatoselectivity in humans.

         


    Five subjects with normal glucose concentrations received either NaB1 L-thyroxyl insulin (B1-T4-Ins) or NPH insulin in a subcutaneous bolus injection, in random order.

         


    Euglycemic clamp and stable isotope dilution techniques were used to evaluate insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake.

        


    B1-T4-Ins was well-tolerated and was rapidly absorbed. The analogue showed high protein-binding capacity(86%) and a long serum half-life.

        


    The duration of action for the analogue was similar to that for NPH insulin, as was the effect on hepatic glucose production.

       


    Less effect on PERIPHERAL glucose uptake was shown by the analogue than by NPH insulin.

       


    The authors conclude that B1-T4-Ins is well tolerated by humans when injected subcutaneously.

      


    The hepatoselectivity of the analogue suggests that B1-T4-Ins has potential to provide greater physiological insulin action than other preparations currently in use.

         

  • AMJ Shapiro, JRT Lakey, et al (Univ. of Alberta, Edmonton, Canada)

    Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive
    Regimen
    .


    N Engl J Med.343: 230-238, 2000

     


    Seven patients studied had type 1 diabetes that was considered severe or uncontrolled despite exogenous insulin administration.

     


    Islet transplantation was done along with glucocorticoid-free immunosuppression immediately thereafter. Intravenous antibiotics were administered prior to transplantation.



    All patients required islets from at least 2 donor pancreases, but all achieved sustained insulin independence soon after transplantation.



    Follow-up ranged from 4.4 to 14.9 months. No episodes of hypoglycemic coma occurred during that time, complications were insignificant and lipid concentrations did not increase
    significantly.

       

  • Adler Al, for the UK Prospective Diabetes Study Group (Univ of Oxford, England)

    Association of Systolic Blood Pressure With Macrovascular and Microvascular Complications of Type 2 Diabetes (UKPDS 36):
    Prospective Observational Study

    BMJ 321: 412-419, 2000

         


    The association between systolic BP over time and the risk of macrovascular and microvascular complications was examined in 4801 patients from 23 hospital-based clinics in England, Scotland, and Northern Ireland. An analysis of relative risk was performed for 3642 participants (white, Asian Indian, and Afro-Caribbean).

        


    It was found that the risk of diabetic complications was strongly correlated with increased BP in patients with type 2 diabetes. Any decrease in BP was likely to decrease the risk of complications, with the lowest risk being in patients with systolic BP below 120 mm Hg.

       

  • Strandberg L-E, Ericsson C-G, O’Konor M-L, et al (Norrtalje Hosp, Sweden; Danderyd Hosp, Sweden; Swedish Natl Board of Health, Stockholm; et al)

    Diabetes Mellitus is a strong Negative Prognostic Factor in Patients With Myocardial Infarction Treated With Thrombolytic Therapy 


    J Intern Med 248: 119-125, 2000

         


    This study included 222 patients (mean age 61 years) who received thrombolytic therapy for suspected acute myocardial infarction in a coronary care unit. 

       


    The outcomes of death or new myocardial infarction were assessed at a mean follow-up of 40 months. 

        


    This study confirmed the prognostic importance of diabetes mellitus. The results support intensive treatment of diabetes during and after myocardial infarction. 

         

  • Stratton IM, for the UK Prospective Diabetes Study Group (Univ of Oxford, England)

    Association of Glycaemia With Macrovascular and Microvascular Complications of Type 2 Diabetes (UKPDS 35): Prospective Observational Study


    BMJ 321: 405-412, 2000

        


    A large group of patients with type 2 diabetes who have achieved a median hemoglobin A1c (HbA1c) of 7% over a median of 10 years was followed up. 

         


    It has been previously shown that tight control of glycemia is associated with fewer microvascular complications compared with patients with less tight control.

        


    The incidence of macrovascular and microvascular complications in this population were examined in this prospective study.

        


    It was found that for patients with type 2 diabetes the risk of complications is strongly related to control of blood glucose levels, the lowest risk being in patients whose HbA1c levels were near normal (less than 6%). Even a modest reduction in glycemia is therefore likely to prevent morbidity and mortality associated with type 2 diabetes.

           

  • Yki-Jarvinen H, for the HOE 901/3002 Study Group (Univ of Helsinki; et al)

    Less Nocturnal Hypoglycemia and Better Post-dinner Glucose Control With Bedtime Insulin Glargine Compared With Bedtime NPH Insulin During Insulin Combination Therapy in Type 2 Diabetes


    Diabetes Care 23: 1130-1136, 2000

         


    Insulin glargine is a human insulin analogue created by recombinant DNA technology. Addition of arginine to the B-chain and a substitution of asparagine with glycine in position A21 in the insulin molecule cause a shift in the isoelectric point, resulting in delayed absorption and a prolonged duration of action. 

         


    In this study of 426 patients the efficacy and safety of glargine insulin were compared with those of NPH insulin in patients with type 2 diabetes poorly controlled by oral agents. 

         


    It was found that bedtime administration of insulin glargine caused less nocturnal hypoglycemia and improved postdinner glycemic control compared with NPH insulin.

          


    Insulin glargine appears to have a longer duration of action than NPH insulin. It is well tolerated and its efficacy makes it a better candidate for use in insulin combination regimens in patients with type 2 diabetes.  

        

  • J Rosenstock for the US Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group (Dallas Diabetes and Endocrine Ctr).

    Basal Insulin Glargine (HOE 901)Versus NPH Insulin in Patients with Type 1 Diabetes on Multiple Daily Insulin Regimens.

    Diabetes Care 23: 1137-1142, 2000

        


    Insulin glargine (HOE 901) is a human insulin analogue synthesized by recombinant DNA technology using Escherichia coli plasmid DNA. Modification of its isoelectric point results in a slower absorption rate and an increased duration of action resembling normal basal insulin secretion.

        


    The subjects, in this trial were 256 patients (mean age 37.5 yrs) with type I diabetes.

         


    Once a day insulin glargine administered for 4 weeks as part of a basal-bolus multiple daily insulin regimen was found more effective than NPH insulin in lowering fasting plasma glucose (FPG) levels in patients with type 1 diabetes.

         


    Insulin glargine could be used at a lower dose than NPH insulin and avoid increase in FPG levels between 5 and 8 AM that occurs with NPH insulin. No significant adverse effects were reported.

         

  • H Pijl, S Ohashi, M Matusda, et al (Univ of Texas, San Antonio; Ergo Sciences Corp, Charlestown, Mass)

    Bromocriptine : A Novel Approach to the Treatment of Type 2 Diabetes.

    Diabetes Care 23: 1154-1161, 2000

         


    In animal models of obesity and diabetes, bromocriptine was found to improve glucose tolerance and insulin resistance. This prompted the authors to evaluate the effects of a quick-release formation of bromocriptine on glucose homeostasis and insulin sensitivity in 22 patients with obesity and type 2 diabetes.

         


    This was a double-blind study of 16 weeks’ duration. Fifteen patients received a quick-release bromocriptine formulation, while 7 patients received placebo.

         


    The bromocriptine group showed significantly lower HbA1c and fasting glucose levels. During oral glucose tolerance testing the mean plasma glucose concentration was reduced significantly with bromocriptine but increased with placebo.

         


    The improved glycemic control induced by bromocriptine was associated with enchanced maximally stimulated insulin-mediated glucose disposal.

         

  • D. Panarotto, J-L Ardilouze, D Tessier, et al (Universite de Sherbrooke, Quebec, Canada)

    The Degree of Hyperinsulinemia and Impaired Glucose Tolerance Predicts Plasma Leptin Concentrations in Women only: A New Exploratory Paradigm.


    Metabolism 49:1055-1062, 2000

         


    Obesity is associated with elevated leptin levels. Plasma levels of leptin correlate positively with obesity and insulin resistance. For a given body mass index (BMI), women have dramatically higher plasma leptin levels than men.

         


    In this study of 48 adults (27 men and 21 women), eighteen subjects were normal, 13 had impaired glucose tolerance (IGT) and 17 had newly diagnosed type 2 diabetes mellitus (DM).

        


    Plasma leptin, glucose and insulin levels were measured before and after a standard 2-hr 75-g oral glucose tolerance test (GTT) following a 12 hr fast.

        


    It was found that ambient plasma glucose and insulin concentrations appear to strongly influence plasma leptin levels in women. Hyperglycaemia (either fasting or postprandial) interferes with insulin’s stimulation of leptin synthesis in women only.

         


    The present study also demonstrated that IGT and type 2 DM are associated with lower leptin levels.

          

  • FJ Berends, MA Cuesta, G Kazemier, et al (Univ. Hosp. Rotterdam Dijkzigt, The Netherlands; Vrije Universiteit, Amsterdam)

    Laparoscopic Detection and Resection of Insulinomas

    Surgery 128: 386-391, 2000

       


    This article reviews a 3-year experience of 10 patients requiring surgery for organic hyperinsulinism caused by solitary insulinomas.

        


    8 women and 2 men underwent laparoscopic US to localize the insulinomas.

        


    Laparoscopic resection was possible in 6 patients by enucleation in 5 and by resection of the pancreatic tail in one.

        


    The remaining patients required conversion to open laparotomy, 3 because the tumour was located too near the portal vein or pancreatic duct and one patient, because the tumour could not be localized.

        


    The authors feel the technique is safe, with low morbidity and a quick recovery time.

         

  • S Akazawa, F Sun et al (Nagasaki Univ, Japan)

    Efficacy of Troglitazone on Body Fat Distribution in Type 2 diabetes.

    Diabetes Care 23, 1067-1071, 2000

        


    Troglitazone, a thiazolidinedione (TZD) derivative is one of a new class of orally active drugs that enhance the action of insulin.

        


    TZD has been found effective in animal models against abnormal glucose and lipid metabolism associated with insulin resistance through the reduction of peripheral insulin resistance.

        


    Mediation of the insulin-sensitizing action of troglitazone may occur through the activation of peroxisome proliferation-activated receptor-g (PPAR-g).

        


    Over a period of 1 year, 20 patients with type 2 diabetes (who had unsatisfactory glycemic control from diet and sulfonylurea therapy and whose insulin secretory capacity was preserved ) were administered a dose of 400mg/d of troglitazone. HbA1c values were significantly decreased over the one-year of treatment, with the lowest values at 4 to 6 months, but body weight was significantly increased.

        


    The authors conclude that predominant accumulation of subcutaneous (SC) fat was an important predictor of the efficacy of troglitazone therapy.

        


    Troglitazone demonstrated greater efficacy in women, who had greater accumulation of SC adipose tissue than did men.

          

  • P Kekäläinen, H Sarlund, M Laakso (Kuopio Univ, Finland; Kuopio City Hosp, Finland)

    Long-term Association of Cardiovascular Risk Factors With Impaired Insulin Secretion and Insulin Resistance.

    Metabolism 49: 1247-1254, 2000.

        


    Association between cardiovascular (CV) risk factors and impaired insulin secretion was investigated in an 8-year prospective population study of research subjects without diabetes.

         


    CV risk factors of 271 participants were analyzed. Insulin sensitivity and acute-phase insulin secretion were assessed.

        


    This trial showed that dyslipidemia, high blood pressure, and uric acid are associated with insulin resistance. High systolic BP and VLDL cholesterol are associated with impaired first-phase insulin secretion.

        


    All the major CV risk factors are associated with insulin resistance. However the significance of the association of systolic B.P and VLDL cholesterol with impaired acute first-phase insulin secretion remains unknown.

          

  • EK Hoogeveen, PJ Kostense, C Jakobs, et al (Vrije Universiteit, Amsterdam)

    Hyperhomocysteinemia Increases Risk of Death, Especially in Type 2 Diabetes: 5 year Follow-up of the Hoorn Study.

    Circulation 101: 1506-1511, 2000

         


    Diabetes and hyperhomocysteinemia (HH) are independently known as risk factors for developing cardiovascular (CV) disease.

         


    A combination of type 2 diabetes and hyperhomocysteinemia (HH) may interact to significantly increase the threat of death of CV disease.

         


    In this study, serum samples were obtained from 2484 patients aged 50 to 75 years. Fasting serum total homocysteine levels were measured in the samples from 171 patients who died and 640 survivors who served as a control group.

        


    The authors conclude that the presence of hyperchromocysteinemia increases the risk of death among patients with diabetes compared to non-diabetic subjects.

        

 



 

 

Speciality Spotlight

 

 
Endocrinology
   

  

Diabetes
        

  • Mayer-Davis EJ, for the IRAS Investigators [Univ of South Carolina, Columbia: Wake Forest Univ. Winston-Salem, NC; Permanente Med Group Inc, Oakland, calif; et al]
    Intensity and Amount of Physical Activity in Relation to Insulin Sensitivity: The Insulin Resistance Atherosclerosis Study
    JAMA 279: 669-674, 1998
          
    After an intravenous glucose tolerance test insulin sensitivity was used to compare the exercising and non-exercising groups.
       

  • Michael F Greene, Massachusetts General Hospital Boston.
    Oral Hypoglycemic Drugs for Gestational Diabetes
    N Engl J Med 2000; 343(16), 19 October 2000, pg. 1178
       
    Early experience with first-generation sulfonylurea drugs such as tolbutamide and chlorpropamide included numerous cases of profound and prolonged hyperinsulinemic hypoglycemia among neonates.
       
    In studies in vitro, the authors demonstrated that glyburide did not cross the human placenta to any appreciable extent, but the same was not true for other sulfonylurea drugs. The concern about the transplacental effects of other sulfonylurea drugs therefore remains.
          

  • Oded Langer, Deborah L Conway, Michael D Berkus, Elly M.-J. Xenakis and Olga Gonzales.
    A Comparison of Glyburide and Insulin in Women with Gestational Diabetes Mellitus.
    N Engl J Med 2000; 343:1134-8.
      
    Women with gestational diabetes (diabetes in pregnant women) are not treated with sulphonylurea drugs because of concern about teratogenicity and neonatal hypoglycaemia. Sulphonylurea drugs cross the placental barrier. As a result there is a chance of teratogenicity. Also the hypoglycaemic action in the new born is quite severe and may produce hypoglycaemic ill-effects in the newborn. The new sulphonylurea called glyburide does not cross the placental barrier.
       
    The adverse reactions in the newborn are therefore avoided and control of diabetes in the mother is as good as with insulin. Both in terms of efficacy and adverse reactions there is no statistical significant difference.
        

  • R Turner, for the UK Prospective Diabetes  Study Group (Radcliffe Infirmary, Oxford, England)
    Tight Blood Pressure Control and Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS 38.
    Bmj 317: 703-713, 1998.
        
    Editors comment: It is possible that the benefit of treatment with ACE inhibitors of diabetic nephropathy is more due to tight control of blood pressure which is achieved by addition of ACE inhibitors than the ACE inhibitors itself.
        

  • Osei Kwame – Diabetes
    YB of Endocrinology, 2000, p.339
        
    Introduction :
    Diabetes mellitus has become a global epidemic. It is projected that by 2025 diabetes will afflict 300 million people worldwide. The driving force for this global epidemic is an increasingly sedentary lifestyle and, consequently, obesity. The introduction of a new classification, with fasting plasma glucose used as a diagnostic tool (with lower fasting glucose levels of 126 mg/dL), was geared toward increasing the rates of early diagnosis. It has the potential of preventing long-term complication of the disease and its attendant morbidity and mortality.
        
    It has been demonstrated that tight glycemic control is beneficial in patients with both type 1 and type 2 diabetes. During the past 25 years, morbidity associated with cardiovascular diseases continued to decline in non-diabetic populations; those with diabetes, especially females, continued to experience increasing morbidity and mortality from cardiovascular diseases. This calls for new emphasis on aggressive triple therapy for patients with diabetes: normalize glucose, blood pressure, and atherogenic profile.
       

  • Pittet D, Wyssa B, Herter-Clavel C, et al [Univ Hosp of Geneva, Switzerland]
    Outcome of Diabetic Foot Infections Treated Conservatively : A Retrospective Cohort Study with Long-term Follow-up
    Arch Intern Med 159: 851-856, 1999
        
    Diabetic foot lesions are the cause of more hospitalizations than any other complications of diabetes. Effective guidance needs to be enunciated to minimize human and financial cost of diabetic foot lesions. A 5-year retrospective cohort study with prospective long-term follow up was undertaken to identify criteria predictive of failure of conservative treatment of such lesions.
        
    The Wagner classification system was used for this study. Variables examined included patient demographics, infection and diabetes.
        
    Of 120 patients, 74% had contiguous osteomyelitis, deep tissue involvement or gangrene. 13% underwent immediate amputation.  Of the remaining, conservative treatment was successful in 63% of cases. 21 of 26 [81%] with skin ulcers. 35 of 50 [70%] with deep tissue infection or suspected osteomyelitis and 1 of 15 [7%] with gangrene.
       
    Independent factors predictive of failure were fever, elevated creatinine, prior hospitalization for diabetic foot lesion, duration of diabetes.
       
    Conservative measures including prolonged culture guided parenteral or oral antibiotics was successful without amputation in 63% of diabetic foot lesion.
         

  • Hoffman J, Spengler M [Clinical Research Collaborative Study Group, Essen, Germany: Bayer AG, Leverkusen, Germany
    Efficacy of 24-Week Monotherapy With Acarbose, Metformin, or Placebo in Dietary-treated NIDDM patients – The Essen -II Study
    Am J Med 103: 483-490, 1997
       
    This is the first article to compare the efficacy of acarbose and metformin in the treatment of NIDDM, with placebo control. All the subjects of study were on a diet control regime only between the ages of 37 and 70 years. 
       
    Dose of acarbose was 100 mgm tablet thrice a day orally with food; metformin was given as 850 mgm tablet twice a day.
       
    Acarbose in addition to reducing blood glucose levels also reduced cholesterol levels, whereas metformin acts only on the former. Lactic acidosis reported with metformin seems not to occur with acarbose.
       

  • Diabetes Mellitus-Miscellaneous
    Levetan CS, Passaro M, Jablonski K, et al [Medlantic Research Inst, Washington, DC; Washington Hosp Ctr, Washington, DC]
    Unrecognized Diabetes among Hospitalized Patients
    Diabetes Care 21: 246-249, 1998
       
    Missing diabetes in patients admitted for other disorders is not uncommon. Glucose levels in the range around 200 mg/dL is often ascribed to infections or stress. Early detection of disease may lead to prevention of subsequent complications, hence all such hyperglycemias need to be investigated.
       
        

  • Andrew J Krentz, Clifford J Bailey et al
    Thiazolidinediones for type 2 diabetes
    New agents reduce insulin resistance but need long term clinical trials
    BMJ, Vol.321, July 29, 2000, pg. 252-253
      
    Insulin resistance (reduced action of insulin) is a prominent defect in type 2 diabetes. Before the introduction of troglitazone in 1997 metformin was the only drug able to sensitize target tissues to insulin. Troglitazone is superseded by more potent agents, rosiglitazone and pioglitazone. 

    Patients with insulin resistance have elevated serum TG and low HDL. This dyslipidemia contributes to risk of atherosclerotic cardiovascular disease. Thiazolidonediones increase HDL and rosiglitazone protects against endothelial dysfunction, lowers BP in insulin resistant and hypertensive rats.

    Clinical trials show that combination therapy using a thiazolidinedione with metformin (main action of which is to reduce glucose production by liver) or a sulphonylurea is particularly effective in lowering glucose concentrations.

    Extensive use of rosiglitazone and pioglitazone has produced little evidence that it has caused hepatic impairment. They are contraindicated in patients with liver damage. Cardiac failure is a contraindication and patients with reduced cardiac reserve need close monitoring. Pioglitazone induces cytochrome P450 (isoform CYP3A4) and the possibility of drug interactions e.g. with oral contraceptives.
      

  • Irene M Stratton, Amanda I Adler, et al 
    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
    BMJ, Vol.321, Aug.12, 2000, pg.405-412.
      
    The objective of the study was to determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complication in patients with type 2 diabetes. It was carried out in 4585 Asian Indian, white and Afro-Caribbean UKPDS (UK prospective diabetes study) patients. Incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbAtc was associated with reductions of risk of 21% for any end-point related to diabetes. The lowest risk being in those with HbAtc values in the normal range (<60%).
       

  • Editorial – Jaakko Tuomilehto
    Controlling glucose and blood pressure in type 2 diabetes. 
    Starting treatment earlier may reduce complications.
    BMJ. Vol.321, Aug.12, 2000, pg.394-395.
      
    The main questions have been when should we start treatment, what is the target level during treatment and what is the best method of treatment, since there are no obvious cut-off points for B.P. or glucose or cholesterol concentrations that would guide clinical decisions.

    Comparisons with observational data have shown that antihypertensive drugs reduce the risk of stroke as predicted, but the reduction in the risk of myocardial infarction is less than expected. Treatment of hypercholesterolaemia with statins reduces the risk of myocardial infarction as predicted, whereas the effect on the risk of stroke seems larger than expected.
      
    The results of UKPDS studies reveal that patients with type 2 diabetes whose hypertension is tightly controlled reduce their risk of macrovascular complications to a greater extent than estimated. The data clearly show that there are no natural thresholds under which the risk of microvascular and macrovascular complications in diabetes are fully prevented but the risk increases steadily with rising levels of risk factors. The lower the level of blood glucose, HbAtcc, or BP, the lower the risk of complications.

    It is difficult to maintain reductions in glucose concentrations and BP even when using multiple drugs that in short term trials have produced excellent results. This was also confirmed in the UKPDS. Thus, the alternative possibility would be to start treatment at lower levels than those currently used as thresholds.

    A large European epidemiological study showed that postprandial glucose concentration is a better predictor of mortality than is fasting glucose. Perhaps impaired glucose tolerance should be an indication for treatment. There is a need to carry out controlled clinical trials to find out whether lowering glucose concentrations at the levels of impaired glucose tolerance will reduce microvascular and macrovascular complications
      

  • A M James Shapiro, Jonathan R.T.Lakey et al 
    Islet transplantation in seven patients with type I diabetes mellitus using a glucocorticoid – free immunosuppressive regimen.
    New Eng J Med. Vol.343, July 27, 2000, pg.230
       
    Seven consecutive patients with type I diabetes and a history of severe hypoglycaemia and metabolic instability underwent islet transplantation in conjunction with a gluco corticoid free immuno suppressive regimen consisting of sirolimus, tacrolimus and daclizumab. Islets were isolated by ductal perfusion with cold purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolisation.

    Authors’ observations were that in patients with type I diabetes, islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid free immunosuppression is combined with the infusion of an adequate islet mass.
      

  • Editorial _ R Paul Robertson
    Successful islet transplantation for patients with diabetes – fact or fantasy ?
    New Eng J Med. Vol.343, July 27, 2000, pg.289-290.
      
    Shapiro and colleagues report 7 transplant recipients with type I diabetes who received an average of 800,000 islets maintained normoglycaemia and glycosylated haemoglobin values without exogenous insulin for an average of 1 year. The key to this impressive outcome include transplanting islets of very high quality as soon as possible after harvest from cadaveric donors and modifying conventional immunosuppressive regimen. Modifications involved eliminating glucocorticoids, using a low dose of tacrolimus and a conventional dose of sirolimus and adding daclizumab. Glucocorticoids and tacrolimus are known to affect beta cell function and survival adversely. It is possible that these 2 drugs and cyclosporine, which formed the usual regimen in prior trials, were the likely culprits leading to islet failure.

    Currently, transplantation of whole pancreas results in insulin independence and normalisation of glycosylated haemoglobin values for 3 years in 70-80% of patients. The less invasive procedure of islet transplantation should take precedence.
        

  •  Journal Scan
    Basic Research
    Heart 2001; 85:373-374

    The glitazones, which are effective anti-diabetic agents, may actually be antiatherogenic. By changing the biochemical pathway of peroxisome proliferator activated receptors (PPAR), the glitazones cause stimulation of a LDL scavenger receptor, SR-A. This may help in lowering the accumulation of lipids in macrophages.
        

  • General Cardiology
    Diabetic heart disease: clinical considerations
    Heart 2001; 85: 463.

    Coronary heart disease in diabetics is slightly different than in a non-diabetic because of autonomic neuropathy. Symptoms are comparatively mild. Atherosclerosis is more different and widespread in diabetes. However response to medical treatment is at least as good as in non-diabetes.
        
    From the surgical point of view, angioplasty and bypass is more difficult in diabetics because of the diffused nature of obstruction in the coronary arteries. However, bypass surgery is to be preferred to angioplasty. ACE inhibitors are of particular value in diabetics and coronary heart diseases, because this group of drugs minimises microvascular complications both in heart and the kidney.
         

  • Balkau B, Shipley M, Jarrett RJ, et al [INSERM, Villejuif, France; Univ of Kuopio, Finland; Univ College Med School, London; et al ]
    High Blood Glucose Concentration is a Risk Factor for Mortality in Middle-aged 
    Nondiabetic Men : 20-Year Follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study

    Diabetes Care 21: 360-367, 1998
       
    High blood glucose levels not tantamount to a diagnosis of diabetes were evaluated as risk factors involved in causation of death due to all causes. Men between 44-55 years were given a standard 2 hour glucose tolerance test and followed up for 20 years. The total was made up of 10,025 in the Whitehall Study, 6629 in the Paris group and 631 in the Helsinki police men. Deaths from cardiovascular disease, coronary heart disease [CHD] and neoplasms were evaluated.
       
    Policemen had the maximum incidence in the all cause group except neoplasms. Deaths from cardiovascular and CHD were more than would be expected. Information of this type may suggest early control of glucose levels.
        
  • Landau Z [Kaplan Hosp, Rehovot Israel]
    Topical Hyperbaric Oxygen and Low Energy Laser for the Treatment of Diabetic Foot Ulcers
    Arch Orthop Trauma Surg 117: 156-158, 1998 
       
    50 diabetic subjects had nonhealing foot ulcers of 9 months mean duration. 15 received topical hyperbaric oxygen alone and 35 in addition were given low energy laser. 25 treatments over a period of 3 months resulted in curing 43 ulcerated feet.
        
  • Endocrine-Miscellaneous
    Bartalena L, Marcocci C, Bogazzi F, et al [Istituto di Endocrinologia, Pisa, Italy; Clinica Oculistica, Pisa, Italy; Univ of Pisa, Italy; et al]
    Relation Between therapy for Hyperthyroidism and the Course of Graves’ Ophthalmopathy
    N Engl J Med 338: 73-78, 1998
       
    443 patients of ‘Graves’ disease were treated with methimazole for 3 to 4 months. Radiotherapy [120 to 150 (G ] for 18 months radioiodine and prednisone [ 0.4 to 0.5 mg/kg] for 3 months were given to some and methimazole was continued for others.
        
    Opthalmopathy began or became worse in 6 months of treatment with radioiodine alone. This was observed in 23 of the 150 subjects. Those who smoked outnumbered the non-smokers. 140 subjects treated with radioiodine and prednisone revealed either regression of ocular changes or non development of such changes if they had none at the onset. In the group of 148 on methimazole 3/74 with ocular changes improved, four developed them or became worse. 141 maintained their status quo.
        
    This study is important as it emphasizes the role of autoimmunity in the pathogenisis of opthalmopathy in hyperthyroidism thus bringing out the role of a corticosteriod in both prevention and therapy of the evolved state
         

  • Hannele Yki-Jarvinen (Dept. of Medicine, Univ. of Helsinki, Helsinki, Finland)
    Management of Type 2 Diabetes Mellitus and Cardiovascular Risk
    Drugs Nov.2000; 60(5)p. 975-983
      
    Very often NIDDM (type 2 diabetes) is associated with hypertension. The disease carries increased risk of microvascular and macrovascular complications. It has now been shown that treatment of hyperglycemia is very effective in reducing microvascular disease but is not so effective in reducing macrovascular disease such as myocardial infarction, stroke and diabetic foot. The authors postulate that prevention of macrovascular disease is much more effectively treated by controlling hypertension, hypercholesterolaemia and small doses of aspirin.
        

  • Ian W Campbell, Victoria Hospitla, Kirkcaldy, Fife, Scotland 
    Antidiabetic Drugs Present and Future
    Will Improving Insulin Resistance Benefit Cardiovascular Risk in Type 2 Diabetes Mellitus?
    Drugs Nov.2000, 60(5), 1017-1028
      
    This survey in Scotland has revealed that treatment with sulfonylureas and insulin reduced only microvascular complication of diabetes but not the macrovascular complications. The only drugs, which possibly may be of benefit in reducing macrovascular complications are metformin and the glitazone group of insulin sensitizers. In addition, the statins would be of great use in the treatment of dyslipidaemia. Metformin particularly reduces glycosylated haemoglobin levels and reduces diabetes related risk and death by more than 36%. Metformin also reduces triglycerides and LDL cholesterol and slightly increases HDL. Pioglitazone also increases HDL cholesterol.
      

  • PG Tawalkar
    Editorial – The Diabetic Foot
    JAPI, Vol.49, May 2001, p. 509
        

    The diabetic foot is one of the commonest complications of diabetes. The major factors involved in the causation are ischemia, neuropathy and infection. Delayed wound healing, dyslipidemias and tobacco worsen the problems in addition to impaired sensation. The dry fissured skin is the portal of entry for microorganisms and can lead to osteomyelitis. Very vigorous antibiotic treatment is required for diabetic foot infections, and surgical incision and drainage are important. Needless to say that control of blood glucose is important but surgical procedures should start even before complete blood sugar control.
       

  • C J Ostgren, U Lindblad, J Ranstam, et al (Malmo Univ. Sweden; Odeshog Health Care Centre Sweden; Skaraborg Inst, Skovde, Sweden; et al)
    Associations Between Smoking and
    b-Cell Function in a Non-hypertensive and Non-diabetic Population: Skaraborg Hypertension and Diabetes Project.
    Diabetic Med 17: 445-450, 2000.
         
    Smoking increases the risk of type-2 diabetes, probably by inducing increased insulin resistance and also a direct adverse effect on pancreatic tissue. The effects of smoking on
    b-cell function, excluding the effects of hypertension and diabetes were studied among 874 patients.
         
    This community based analysis of subjects, suggests that smoking may adversely affect b-cell function, at least in men. Smoking also has been associated with increased microvascular disease especially retinopathy.
          

  • L Chaillous, for the Diabetes Insuline Orale Group (Universitaires de Nantes, France; et al)
    Oral insulin administration and residual b-cell function in Recent-Onset type-1 Diabetes: A Multicentre Randomized Controlled Trial.
    Lancet, 356, 545-549, 2000
         
    The study group of 131 auto antibody-positive patients with diabetes was enrolled within 2 weeks of diagnosis.
        
    Oral insulin (2.5mg or 7.5mg) or placebo was given at random to patients for one year, in addition to subcutaneous insulin therapy.
         
    Oral administration of insulin at the doses used in this trial and initiated at the clinical onset of type-1 diabetes did not prevent deterioration of ß-cell function in this group of patients. 
            

  • F. Shojaee-Moradie, A Schuttler et al (King’s College, London etc.)
    Novel Hepatoselective Insulin Analog: Studies with a Covalently Linked Thyroxyl-Insulin Complex in Humans.
    Diabetes Care 23: 1124-1129, 2000
         
    A thyroxyl-insulin analogue with restricted access to receptor sites in peripheral tissues was evaluated to determine whether it displayed relative hepatoselectivity in humans.
         
    Five subjects with normal glucose concentrations received either NaB1 L-thyroxyl insulin (B1-T4-Ins) or NPH insulin in a subcutaneous bolus injection, in random order.
         
    Euglycemic clamp and stable isotope dilution techniques were used to evaluate insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake.
        
    B1-T4-Ins was well-tolerated and was rapidly absorbed. The analogue showed high protein-binding capacity(86%) and a long serum half-life.
        
    The duration of action for the analogue was similar to that for NPH insulin, as was the effect on hepatic glucose production.
       
    Less effect on PERIPHERAL glucose uptake was shown by the analogue than by NPH insulin.
       
    The authors conclude that B1-T4-Ins is well tolerated by humans when injected subcutaneously.
      
    The hepatoselectivity of the analogue suggests that B1-T4-Ins has potential to provide greater physiological insulin action than other preparations currently in use.
         

  • AMJ Shapiro, JRT Lakey, et al (Univ. of Alberta, Edmonton, Canada)
    Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen.
    N Engl J Med.343: 230-238, 2000
     
    Seven patients studied had type 1 diabetes that was considered severe or uncontrolled despite exogenous insulin administration.
     
    Islet transplantation was done along with glucocorticoid-free immunosuppression immediately thereafter. Intravenous antibiotics were administered prior to transplantation.

    All patients required islets from at least 2 donor pancreases, but all achieved sustained insulin independence soon after transplantation.

    Follow-up ranged from 4.4 to 14.9 months. No episodes of hypoglycemic coma occurred during that time, complications were insignificant and lipid concentrations did not increase significantly.
       

  • Adler Al, for the UK Prospective Diabetes Study Group (Univ of Oxford, England)
    Association of Systolic Blood Pressure With Macrovascular and Microvascular Complications of Type 2 Diabetes (UKPDS 36): Prospective Observational Study
    BMJ 321: 412-419, 2000
         
    The association between systolic BP over time and the risk of macrovascular and microvascular complications was examined in 4801 patients from 23 hospital-based clinics in England, Scotland, and Northern Ireland. An analysis of relative risk was performed for 3642 participants (white, Asian Indian, and Afro-Caribbean).
        
    It was found that the risk of diabetic complications was strongly correlated with increased BP in patients with type 2 diabetes. Any decrease in BP was likely to decrease the risk of complications, with the lowest risk being in patients with systolic BP below 120 mm Hg.
       

  • Strandberg L-E, Ericsson C-G, O’Konor M-L, et al (Norrtalje Hosp, Sweden; Danderyd Hosp, Sweden; Swedish Natl Board of Health, Stockholm; et al)
    Diabetes Mellitus is a strong Negative Prognostic Factor in Patients With Myocardial Infarction Treated With Thrombolytic Therapy 
    J Intern Med 248: 119-125, 2000
         
    This study included 222 patients (mean age 61 years) who received thrombolytic therapy for suspected acute myocardial infarction in a coronary care unit. 
       
    The outcomes of death or new myocardial infarction were assessed at a mean follow-up of 40 months. 
        
    This study confirmed the prognostic importance of diabetes mellitus. The results support intensive treatment of diabetes during and after myocardial infarction. 
         

  • Stratton IM, for the UK Prospective Diabetes Study Group (Univ of Oxford, England)
    Association of Glycaemia With Macrovascular and Microvascular Complications of Type 2 Diabetes (UKPDS 35): Prospective Observational Study
    BMJ 321: 405-412, 2000
        
    A large group of patients with type 2 diabetes who have achieved a median hemoglobin A1c (HbA1c) of 7% over a median of 10 years was followed up. 
         
    It has been previously shown that tight control of glycemia is associated with fewer microvascular complications compared with patients with less tight control.
        
    The incidence of macrovascular and microvascular complications in this population were examined in this prospective study.
        
    It was found that for patients with type 2 diabetes the risk of complications is strongly related to control of blood glucose levels, the lowest risk being in patients whose HbA1c levels were near normal (less than 6%). Even a modest reduction in glycemia is therefore likely to prevent morbidity and mortality associated with type 2 diabetes.
           

  • Yki-Jarvinen H, for the HOE 901/3002 Study Group (Univ of Helsinki; et al)
    Less Nocturnal Hypoglycemia and Better Post-dinner Glucose Control With Bedtime Insulin Glargine Compared With Bedtime NPH Insulin During Insulin Combination Therapy in Type 2 Diabetes
    Diabetes Care 23: 1130-1136, 2000
         
    Insulin glargine is a human insulin analogue created by recombinant DNA technology. Addition of arginine to the B-chain and a substitution of asparagine with glycine in position A21 in the insulin molecule cause a shift in the isoelectric point, resulting in delayed absorption and a prolonged duration of action. 
         
    In this study of 426 patients the efficacy and safety of glargine insulin were compared with those of NPH insulin in patients with type 2 diabetes poorly controlled by oral agents. 
         
    It was found that bedtime administration of insulin glargine caused less nocturnal hypoglycemia and improved postdinner glycemic control compared with NPH insulin.
          
    Insulin glargine appears to have a longer duration of action than NPH insulin. It is well tolerated and its efficacy makes it a better candidate for use in insulin combination regimens in patients with type 2 diabetes.  
        

  • J Rosenstock for the US Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group (Dallas Diabetes and Endocrine Ctr).
    Basal Insulin Glargine (HOE 901)Versus NPH Insulin in Patients with Type 1 Diabetes on Multiple Daily Insulin Regimens.
    Diabetes Care 23: 1137-1142, 2000
        
    Insulin glargine (HOE 901) is a human insulin analogue synthesized by recombinant DNA technology using Escherichia coli plasmid DNA. Modification of its isoelectric point results in a slower absorption rate and an increased duration of action resembling normal basal insulin secretion.
        
    The subjects, in this trial were 256 patients (mean age 37.5 yrs) with type I diabetes.
         
    Once a day insulin glargine administered for 4 weeks as part of a basal-bolus multiple daily insulin regimen was found more effective than NPH insulin in lowering fasting plasma glucose (FPG) levels in patients with type 1 diabetes.
         
    Insulin glargine could be used at a lower dose than NPH insulin and avoid increase in FPG levels between 5 and 8 AM that occurs with NPH insulin. No significant adverse effects were reported.
         

  • H Pijl, S Ohashi, M Matusda, et al (Univ of Texas, San Antonio; Ergo Sciences Corp, Charlestown, Mass)
    Bromocriptine : A Novel Approach to the Treatment of Type 2 Diabetes.
    Diabetes Care 23: 1154-1161, 2000
         
    In animal models of obesity and diabetes, bromocriptine was found to improve glucose tolerance and insulin resistance. This prompted the authors to evaluate the effects of a quick-release formation of bromocriptine on glucose homeostasis and insulin sensitivity in 22 patients with obesity and type 2 diabetes.
         
    This was a double-blind study of 16 weeks’ duration. Fifteen patients received a quick-release bromocriptine formulation, while 7 patients received placebo.
         
    The bromocriptine group showed significantly lower HbA1c and fasting glucose levels. During oral glucose tolerance testing the mean plasma glucose concentration was reduced significantly with bromocriptine but increased with placebo.
         
    The improved glycemic control induced by bromocriptine was associated with enchanced maximally stimulated insulin-mediated glucose disposal.
         

  • D. Panarotto, J-L Ardilouze, D Tessier, et al (Universite de Sherbrooke, Quebec, Canada)
    The Degree of Hyperinsulinemia and Impaired Glucose Tolerance Predicts Plasma Leptin Concentrations in Women only: A New Exploratory Paradigm.
    Metabolism 49:1055-1062, 2000
         
    Obesity is associated with elevated leptin levels. Plasma levels of leptin correlate positively with obesity and insulin resistance. For a given body mass index (BMI), women have dramatically higher plasma leptin levels than men.
         
    In this study of 48 adults (27 men and 21 women), eighteen subjects were normal, 13 had impaired glucose tolerance (IGT) and 17 had newly diagnosed type 2 diabetes mellitus (DM).
        
    Plasma leptin, glucose and insulin levels were measured before and after a standard 2-hr 75-g oral glucose tolerance test (GTT) following a 12 hr fast.
        
    It was found that ambient plasma glucose and insulin concentrations appear to strongly influence plasma leptin levels in women. Hyperglycaemia (either fasting or postprandial) interferes with insulin’s stimulation of leptin synthesis in women only.
         
    The present study also demonstrated that IGT and type 2 DM are associated with lower leptin levels.
          

  • FJ Berends, MA Cuesta, G Kazemier, et al (Univ. Hosp. Rotterdam Dijkzigt, The Netherlands; Vrije Universiteit, Amsterdam)
    Laparoscopic Detection and Resection of Insulinomas
    Surgery 128: 386-391, 2000
       
    This article reviews a 3-year experience of 10 patients requiring surgery for organic hyperinsulinism caused by solitary insulinomas.
        
    8 women and 2 men underwent laparoscopic US to localize the insulinomas.
        
    Laparoscopic resection was possible in 6 patients by enucleation in 5 and by resection of the pancreatic tail in one.
        
    The remaining patients required conversion to open laparotomy, 3 because the tumour was located too near the portal vein or pancreatic duct and one patient, because the tumour could not be localized.
        
    The authors feel the technique is safe, with low morbidity and a quick recovery time.
         

  • S Akazawa, F Sun et al (Nagasaki Univ, Japan)
    Efficacy of Troglitazone on Body Fat Distribution in Type 2 diabetes.
    Diabetes Care 23, 1067-1071, 2000
        
    Troglitazone, a thiazolidinedione (TZD) derivative is one of a new class of orally active drugs that enhance the action of insulin.
        
    TZD has been found effective in animal models against abnormal glucose and lipid metabolism associated with insulin resistance through the reduction of peripheral insulin resistance.
        
    Mediation of the insulin-sensitizing action of troglitazone may occur through the activation of peroxisome proliferation-activated receptor-g (PPAR-g).
        
    Over a period of 1 year, 20 patients with type 2 diabetes (who had unsatisfactory glycemic control from diet and sulfonylurea therapy and whose insulin secretory capacity was preserved ) were administered a dose of 400mg/d of troglitazone. HbA1c values were significantly decreased over the one-year of treatment, with the lowest values at 4 to 6 months, but body weight was significantly increased.
        
    The authors conclude that predominant accumulation of subcutaneous (SC) fat was an important predictor of the efficacy of troglitazone therapy.
        
    Troglitazone demonstrated greater efficacy in women, who had greater accumulation of SC adipose tissue than did men.
          

  • P Kekäläinen, H Sarlund, M Laakso (Kuopio Univ, Finland; Kuopio City Hosp, Finland)
    Long-term Association of Cardiovascular Risk Factors With Impaired Insulin Secretion and Insulin Resistance.
    Metabolism 49: 1247-1254, 2000.
        
    Association between cardiovascular (CV) risk factors and impaired insulin secretion was investigated in an 8-year prospective population study of research subjects without diabetes.
         
    CV risk factors of 271 participants were analyzed. Insulin sensitivity and acute-phase insulin secretion were assessed.
        
    This trial showed that dyslipidemia, high blood pressure, and uric acid are associated with insulin resistance. High systolic BP and VLDL cholesterol are associated with impaired first-phase insulin secretion.
        
    All the major CV risk factors are associated with insulin resistance. However the significance of the association of systolic B.P and VLDL cholesterol with impaired acute first-phase insulin secretion remains unknown.
          

  • EK Hoogeveen, PJ Kostense, C Jakobs, et al (Vrije Universiteit, Amsterdam)
    Hyperhomocysteinemia Increases Risk of Death, Especially in Type 2 Diabetes: 5 year Follow-up of the Hoorn Study.
    Circulation 101: 1506-1511, 2000
         
    Diabetes and hyperhomocysteinemia (HH) are independently known as risk factors for developing cardiovascular (CV) disease.
         
    A combination of type 2 diabetes and hyperhomocysteinemia (HH) may interact to significantly increase the threat of death of CV disease.
         
    In this study, serum samples were obtained from 2484 patients aged 50 to 75 years. Fasting serum total homocysteine levels were measured in the samples from 171 patients who died and 640 survivors who served as a control group.
        
    The authors conclude that the presence of hyperchromocysteinemia increases the risk of death among patients with diabetes compared to non-diabetic subjects.
        

 

 

By |2022-07-20T16:42:15+00:00July 20, 2022|Uncategorized|Comments Off on Diabetes

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