DIABETES
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diagnosis and treatment by a qualified, licensed professional.
Prolonged sulfonylurea-induced hypoglycemia in diabetic patients with end-stage renal disease.
Krepinsky J, Ingram AJ, Clase CM.
Am J Kidney Dis 2000;35:500-505.The results of this study show that diabetic patients with end stage kidney disease who undergo sulfonylurea-based oral hypoglycemic treatment have an increased risk of potentially life-threatening prolonged hypoglycemia. The authors suggest use of different drugs in this group of patients.
Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-Up.
Fisman EZ, et al.
Cardiology 1999;91(3):195-202This study was conducted on 11,440 patients of whom 9,045 were nondiabetics and 2,395 diabetics, all with a history of myocardial infarction and/or stable angina. Diabetic patients had almost twice the risk of death compared to nondiabetics. Among diabetic patients, those on a diet regimen had the lowest mortality rates (18.5%), followed by those on sulfonylureas (22,5%), metformin (25.6%), and combination therapy consisting of metformin and sulfonylureas (31.6%). After adjusting for different variables, use of metformin, alone or in combination, was associated with a 42% increased risk of death. These results indicate that metformin significantly increases mortality rates in diabetic patients with ischemic heart disease.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
UK Prospective Diabetes Study (UKPDS) Group.
Lancet 1998 Sep 12;352(9131):837-53This study shows that intensive treatment of type 2 diabetic patients with sulphonylureas or insulin, compared to conventional treatment (consisting of diet with the addition of pharmacological treatment if glucose levels cannot be controlled by diet alone), decreases the risk of microvascular complications (i.e. retinopathy, nephropathy and neuropathy) but has no effect in preventing macrovascular complications. Furthermore, patients in the intensive treatment group experienced significantly more hypoglycaemic episodes and weight gain compared to those in the standard treatment group. Weight gain was especially high in patients treated with insulin.
Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Diabetes Control and Complications Trial.
Purnell JQ, et al.
JAMA 1998 Jul 8;280(2):140-6.This study conducted on 1169 patients aged 18 and older with type 1 diabetes randomized to receive intensive or standard diabetic treatment, shows that individuals receiving intensive treatment exhibited greater weight gain compared to those on conventional treatment. Weight gain resulted in increased systolic blood pressure and increased levels of triglycerides and total and LDL-cholesterol. The changes in blood pressure and lipid profile associated with intensive diabetes treatment may increase the risk of cardiovascular disease in these patients.
Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction.
Garratt KN, et al.
J Am Coll Cardiol 1999 Jan;33(1):119-24This study shows that diabetic patients taking sulfonylurea drugs undergoing coronary angioplasty after myocardial infarction have a 2.7-fold increased risk of dying, compared to diabetic patients not taking these drugs. Sulfonylureas seem to render the myocardium more susceptible to injury.
Adverse events and their association with treatment regimens in the diabetes control and complications trial.
Diabetes Care 1995 Nov;18(11):1415-27This study was conducted on 1,441 individuals with insulin-dependent diabetes mellitus randomized to receive either intensive or conventional insulin treatment and followed up for a mean of 6.5 years. Intensive treatment did not decrease the incidence of death, major morbidity or ketoacidosis. On the other hand, intensive treatment was associated with a 3-fold increased rate of severe hypoglycemic episodes requiring assistance, and with a 73% higher risk of becoming overweight. The authors note that these results may not reflect the real rate of adverse events due to intensive treatment, since the sample population of this trial consisted of carefully chosen healthy individuals who received frequent clinical evaluation.
Weight gain associated with intensive therapy in the diabetes control and complications trial.
The DCCT Research Group.
Diabetes Care 1988 Jul-Aug;11(7):567-73This article shows that patients receiving intensive treatment for insulin-dependent diabetes mellitus have a higher risk of developing hypoglycemia and of becoming overweight independently of caloric intake or exercise levels. After one year of treatment, patients intensively treated gained 5.1 kg (+/- 4.6 kg) while those conventionally treated gained 2.4 kg (+/- 3.7 kg). Weight gain can adversely affect lipid profile and blood pressure and increase the risk of cardiovascular diseases.
Hypertension in diet versus pharmacologically treated diabetics: mortality over a 5-year follow-up.
Tenenbaum A, et al.
Hypertension 1999 Apr;33(4):1002-7This study evaluated mortality rates over a 5-year follow-up period in a sample population of 9,033 nondiabetics and 2,482 diabetics. Mortality rates were doubled in the diabetic compared to the nondiabetic population (22% vs. 11%). Among diabetics, 987 patients were treated with diet only and 1495 were pharmacologically treated. Among those with normal blood pressure, mortality rates were 14% in patients on diet only, and 24.2% in those treated pharmacologically. Mortality rates in diabetic hypertensive patients were similar in both diet and pharmacologically treated individuals. These results show that mortality rates in diabetic patients with normal blood pressure are significantly lower in the diet versus the pharmacologically treated group.
Intensive therapy and progression to clinical albuminuria in patients with insulin dependent diabetes mellitus and microalbuminuria
Microalbuminuria Collaborative Study Group.
BMJ 1995;311:973-977 (14 October)This study shows that intensive treatment fails to prevent deterioration of renal function in patients with type 1 diabetes and compromised kidney function. This might be due to an increase in blood pressure caused by high levels of insulin. High blood pressure seems to be a more important risk factor than increased blood glucose levels in the progression of renal disease.
Does insulin therapy have a hypertensive effect in type 2 diabetes?
Genev NM, et al.
J Cardiovasc Pharmacol 1998 Jul;32(1):39-41This study evaluated blood pressure in patients with type 2 diabetes before, at 6, and at 12 weeks after initiation of insulin treatment. Systolic blood pressure was significantly increased 12 weeks after initiation of treatment compared to baseline (from a mean value of 134.6 mm Hg to 144.8 mm Hg), and so was diastolic pressure (from 71.9 mm Hg to 74.9 mm Hg). Body mass index was also significantly increased after 12 weeks of treatment. These changes may translate in an increased risk of coronary artery disease associated with long-term treatment.
Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49).
UK Prospective Diabetes Study (UKPDS) Group.
Turner RC, Cull CA, Frighi V, Holman RR.
JAMA 1999 Jun 2;281(21):2005-12This study conducted on 4075 individuals with type 2 diabetes randomized to treatment with diet alone, insulin, sulfonylurea, or metformin, shows that two-to-three times more individuals reached targeted blood glucose concentration with drug treatment compared to diet alone. However, these effects are relatively short lasting, and after 3 years 50% of patients experience deterioration of blood glucose control and necessitate change in treatment.
Issues surrounding tight glycemic control in people with type 2 diabetes mellitus.
Cerveny JD, Leder RD, Weart CW
Ann Pharmacother 1998 Sep;32(9):896-905This review highlights that it is still to be determined whether pharmacological treatment reduces morbidity and mortality from cardiovascular disease in patients with type 2 diabetes.
The effect of glycemic control on the incidence of macrovascular
complications of type 2 diabetes.
Stern MP
Arch Fam Med 1998 Mar-Apr;7(2):155-62This article emphasizes the need for clinical trials to determine whether insulin therapy increases or diminishes the rate of macrovascular complications in diabetic patients.
Diabetes mellitus in older patients. Is tight blood glucose control warranted?
Lunt H.
Drugs Aging 1996 Jun;8(6):401-7.This article reiterates that the evidence demonstrating that improved blood glucose control in patients with type 2 diabetes reduces morbidity and mortality from coronary artery disease is weak. Furthermore pharmacological treatment is associated with potentially fatal complications such as hypoglycemic episodes associated with use of sulphonylureas and insulin, and metformin-induced lactic acidosis.
Mortality and treatment side-effects during long-term intensified
conventional insulin treatment in the Stockholm Diabetes Intervention
Reichard P, Pihl M.
Diabetes, 43(2):313-7 1994 Feb.This study was conducted on 102 diabetic patients randomized to receive intensified (48 patients) or standard (54 patients) insulin treatment. After 7.5 years of follow up, microvascular disease was retarded in patients on intensive treatment. However, 4 patients died in the intensified treatment group (8.4%) while 3 died in the standard group (5.6%). Weight gain was significantly higher in patients on intensive treatment compared to those on standard therapy (4.4 +/- 1.1 kg versus 1.8 +/- 0.7 kg). Furthermore, severe hypoglycemic episodes were significantly more frequent in the intensive versus the standard therapy group (mean of 1.1 episodes per patient per year vs. 0.4 episodes per patient per year, respectively).
Should insulin treatment be avoided? Blood sugar is not everything in type 2 diabetes.
Carlsen SM
Tidsskr Nor Laegeforen, 115(18):2271-5 1995 Aug 10This article emphasizes that high levels of insulin increase the risk of cardiovascular disease and atherosclerosis. Increased insulin levels in type 2 diabetics are associated with increased mortality. The author reports on the results of a pilot study showing that diabetics treated with intensive versus conventional insulin therapy had higher rates of cardiovascular mortality, and suggest that insulin be given only when other drug treatment fail to achieve normal blood glucose levels.
United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy.
United Kingdom Prospective Diabetes Study Group.
Ann Intern Med 1998 Feb 1;128(3):165-75This study shows that 50% of patients treated with insulin for type 2 diabetes and 66% of those on sulfonylureas cannot be longer controlled by the initial drug regimen after 6 years of treatment and require additional therapy.
The sulfonylurea controversy: more questions from the heart.
Brady PA, Terzic A
J Am Coll Cardiol 1998 Apr;31(5):950-6This article emphasizes that sulfonylureas, the most widely used antidiabetic drugs, may be partly responsible for the increase in morbidity and mortality seen in diabetic patients. The first association between this class of drugs and increased death from cardiovascular disease arose 25 years ago and reemerged recently after it was discovered that sulfonylureas inhibit potassium channels in the heart thus lowering myocardial tolerance for injury.
Jollis JG, et al.
Relation between sulfonylurea therapy, complications, and outcome for elderly patients with acute myocardial infarction.
Am Heart J. 1999 Nov;138(5 Pt 1):376-80.
O'Keefe JH Jr, et al.
Sulfonylurea drugs and cardiovascular mortality.
J Am Coll Cardiol. 1999 Sep;34(3):958United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years.
BMJ 1995 Jan 14;310(6972):83-8In this study 2520 individuals with newly diagnosed type 2 diabetes were randomized to treatment with diet only or with the addition of sulfhonylureas, insulin, or metformin. Although patients receiving pharmacological treatment reached lower levels of blood glucose compared to those on diet only, they nevertheless remained hyperglycemic. Patients treated pharmacologically gained significantly more weight than those on diet only, and hypoglycemic episodes were significantly more frequent in patients treated with sulfhonylureas or insulin, compared to those on diet or metformin. Blood insulin levels were higher in the treated versus the diet group. The benefits of decreased blood glucose levels achieved through pharmacological treatment must be weighted against the risk of potentially fatal hypoglycemic episodes, the increase in serum insulin concentration which may contribute to the formation of atheromas, and the increase in body weight and possibly blood cholesterol which may put patients at higher risk for coronary artery disease.
Diabetes drug withdrawn after reports of hepatic events. News
Wise, J.
BMJ 1997;315:1559-1564 (13 December)This article informs on the withdrawal of the diabetic drug Rezulin from the U.K. market less than three months after its release, due to an increasing number of worldwide reports of serious hepatic damage caused by drug. Over 130 individuals have developed severe adverse reactions such as hepatic necrosis and hepatic failure, and 6 have died. The drug was withdrawn because the occurrence of adverse reactions cannot be predicted, and their incidence cannot be properly determined. The U.S. Food and Drug Administration decided to keep the drug on the market provided that patients receive frequent monitoring of liver function and that warnings be included on the information sheet.
According to an article published in the January 16, 1999 issue of the New York Post Rezulin-induced liver failure has caused 32 deaths in the U.S. and Japan. Although the FDA recommended frequent liver testing to detect warning signs of hepatic damage, two individuals who tested fine died within two weeks of being tested due to treatment complications. A trial initiated to determine the effects of the drug in healthy individuals at high-risk of developing diabetes was halted after the death of one participant.
Hepatotoxicity due to troglitazone: report of two cases and review of
adverse events reported to the United States Food and Drug Administration.
Kohlroser J, et al.
Am J Gastroenterol 2000 Jan;95(1):272-6This article reports on two patients who developed liver damage during treatment with the diabetic drug Rezulin. Forty six cases of liver toxicity reported to the U.S. FDA are also presented. Treatment with Rezulin results in hepatotoxicity in approximately 2% of patients. Hepatotoxicity can be severe and even fatal.
Troglitazone-induced hepatic failure leading to liver transplantation. A
Case report.
Neuschwander-Tetri BA, et al.
Ann Intern Med 1998 Jul 1;129(1):38-41This article reports on the case of a 55 year-old woman who developed massive liver necrosis leading to liver failure and liver transplantation after 3.5 months of treatment with the diabetic drug Rezulin. It also presents 5 cases of severe liver damage resulting in liver transplantation and death, reported to the U.S. FDA.
An autopsy case of troglitazone-induced fulminant hepatitis.
Shibuya A, et al.
Diabetes Care 1998 Dec;21(12):2140-3This article reports on the case of a 58-year old man who developed severe hepatitis leading to death 2 months after initiation of treatment with the diabetic drug Rezulin.
MORE ARTICLES ON COMPLICATIONS
DUE TO TREATMENT FOR DIABETES
Troglitazone-associated hepatic failure.
Misbin RI.
Ann Intern Med. 1999 Feb 16;130(4 Pt 1):330.
Severe hepatotoxicity associated with troglitazone.
Herrine SK, et al
Ann Intern Med. 1999 Jan 19;130(2):163-4.
Fatal hepatotoxicity associated with troglitazone.
Vella A, et al.
Ann Intern Med. 1998 Dec 15;129(12):1080.
A Japanese case of liver dysfunction after 19 months of troglitazone treatment.
Iwase M, et al.
Diabetes Care. 1999 Aug;22(8):1382-4.
Hepatic dysfunction associated with troglitazone.
Watkins PB, et al.
N Engl J Med. 1998 Mar 26;338(13):916-7.
Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone.
Gitlin N, et al.
Ann Intern Med. 1998 Jul 1;129(1):36-8.
Deterioration of rheumatoid arthritis with troglitazone: a rare and unexpected adverse effect.
Sakurai A, et al.
Arch Intern Med. 2000 Jan 10;160(1):118-9. No abstract available.
Pleuropulmonary disease in a man with diabetes who was treated with
troglitazone.
Koshida H, et al.
N Engl J Med. 1998 Nov 5;339(19):1400-1.
Pulmonary edema associated with troglitazone therapy.
Hirsch IB, et al.
Arch Intern Med. 1999 Aug 9-23;159(15):1811.
Significant weight gain with rezulin therapy.
Gorson DM.
Arch Intern Med. 1999 Jan 11;159(1):99.
Biguanide-associated lactic acidosis. Case report and review of the literature.
Gan SC; Barr J; Arieff AI; Pearl RG
Arch Intern Med, 152(11):2333-6 1992 NovThis article emphasizes the risk of severe lactic acidosis associated with use of biguanides, a commonly used class of antidiabetic drugs. Members of the biguanides include metformin, buformin and phenformin. The latter drug was withdrawn from the U.S. market in 1976 because of its likely association with lactic acidosis. However such risk exists also for the other biguanides, as this article shows by presenting a case of severe lactic acidosis in a patient taking metformin.
Clinical risk associated with contrast angiography in metformin treated patients: a clinical review.
Nawaz S; Cleveland T; Gaines PA; Chan P
Clin Radiol, 53(5):342-4 1998 MayThis study emphasizes the dangers of performing angiography with iodinated contrast agents in diabetic patients using metformin with underlying renal disease. Such patients are at increased risk of developing metformin-induced lactic acidosis. The case of 33 diabetic patients who underwent contrast angiography is presented. Four of them had signs of renal dysfunction prior to the procedure, and all four of them deteriorated and died following the procedure. Two patients had documented lactic acidosis. The authors conclude that their experience does not provide support to current guidelines recommending use of contrast angiography in diabetic patients with impaired renal function taking metformin, and propose discontinuation of the drug before proceeding with angiography
Lactic acidosis in patients with diabetes treated with metformin [letter]
Misbin RI; Green L; Stadel BV; Gueriguian JL; Gubbi A; Fleming GA
N Engl J Med, 338(4):265-6 1998 Jan 22
Non-steroidal anti-inflammatory drugs and metformin: a cause for concern?
Chan NN; Fauvel NJ; Feher MD, Letter
Lancet, 352(9123):201 1998 Jul 18
Survival after metformin-associated lactic acidosis in peritoneal dialysis--dependent renal failure.
Schmidt R; Horn E; Richards J; Stamatakis M
Am J Med, 102(5):486-8 1997 May
Metformin-associated lactic acidosis.
Pearlman BL; Fenves AZ; Emmett M
Am J Med, 101(1):109-10 1996 Jul
Metformin-associated lactic acidosis.
Hulisz DT; Bonfiglio MF; Murray RD
J Am Board Fam Pract, 11(3):233-6 1998 May-Jun
