Antidiabetic agents

BACKGROUND: Diabetes has been associated with an increased risk of hepatocellular carcinoma (HCC) in studies of referred patients. This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC. METHODS: We used the Surveillance Epidemiology and End-Results Program (SEER)-Medicare linked database to identify patients aged 65 years and older diagnosed with HCC and randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index date were examined. Inpatient and outpatient claims files were searched for diagnostic codes indicative of diabetes, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease, and haemochromatosis. HCC patients without these conditions were categorised as idiopathic. Unadjusted and adjusted odds ratios were calculated in logistic regression analyses. RESULTS: We identified 2061 HCC patients and 6183 non-cancer controls. Compared with non-cancer controls, patients with HCC were male (66% v 36%) and non-White (34% v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis), diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjusted odds ratio for diabetes declined but remained significant (adjusted odds ratio 2.87 (95% confidence interval 2.49-3.30)). A significant positive interaction between HCV and diabetes was detected (p<0.0001). Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. CONCLUSIONS: Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independent risk factor for HCC.

The many studies on oxidative stress, antioxidant treatment, and diabetic complications have shown that oxidative stress is increased and may accelerate the development of complications through the metabolism of excessive glucose and free fatty acids in diabetic and insulin-resistant states. However, the contribution of oxidative stress to diabetic complications may be tissue-specific, especially for microvascular disease that occurs only in diabetic patients but not in individuals with insulin resistance without diabetes, even though both groups suffer from oxidative stress. Although antioxidant treatments can show benefits in animal models of diabetes, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating complications. Furthermore, it appears that oxidative stress is only one factor contributing to diabetic complications; thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

AIM: Short-term efficacy of glimepiride, metformin and pioglitazone in newly diagnosed type 2 diabetes was compared with a group treated with diet and exercise. Effects on insulin secretion and sensitivity were also assessed. METHODS: New type 2 diabetic subjects, aged 30-60 years with BMI < 30 kg/m2 were selected. Subjects having glycosylated haemoglobin (HbA1c) of < 8.5% were advised diet and exercise (control group). Others having HbA1c > or = 8.5 to 11.0% were randomized to receive glimepiride (group 2), metformin (group 3) and pioglitazone (group 4). At the final review between 12-14 weeks, changes in plasma glucose, HbA1c, lipid profile, HOMA insulin resistance (HOMA-IR), beta cell function (HOMA-BF) and insulinogenic index (delta I/G) were measured. Comparisons were made using appropriate statistical analyses. RESULTS: Seventy-seven of the 97 subjects randomized equally into four groups, were available for review. Glycaemic parameters improved in all groups. Mean cholesterol decreased significantly in groups treated with metformin and pioglitazone. HDL-cholesterol increased with pioglitazone. Insulin resistance decreased significantly with metformin and pioglitazone, beta cell fuhction also showed improvement CONCLUSIONS: Glycaemic control was seen in all study groups, the improvement was better in drug treated groups than in the control group. Glimepiride improved insulin secretion including the early phase secretion and reduced plasma triglycerides. Metformin and pioglitazone had beneficial effects on lipid levels, improved insulin sensitivity and improved insulin secretion also.

Diabetes mellitus can be a devastating lifelong disease if not treated appropriately. The physician and the patient should be aware of both extremes involved with DM: hyperglycemia and hypoglycemia. Patient education and preventive care are perhaps more important in this disease than many others. A multidisciplinary approach involving the patient, physician, and diabetic educator is best to assure a better quality of life. Enormous advances in the treatment of diabetes have occurred over the past decade and even greater ones can be expected in the future. New drugs, insulin delivery devices, and noninvasive glucose monitoring machines have the potential to normalize blood sugar levels and return diabetics to a near normal lifespan without complications.

Postgrad Med. 2003 May;Spec No:35-44.
Beneficial effects resulting from thiazolidinediones for treatment of type 2 diabetes mellitus.
Bell DS.
University of Alabama at Birmingham, School of Medicine, Department of Medicine, Birmingham, USA.

Because new drugs continue to be developed, physicians treating patients with type 2 diabetes have a wide range of agents from which to choose. The newest class, the thiazolidinediones (TZDs), should be a mainstay of treatment for most patients with type 2 diabetes, because these agents reduce insulin resistance as well as improve glycemic control. Patients with the insulin resistance syndrome are at increased risk for developing cardiovascular disease. However, decreasing insulin resistance with TZD use may reduce the incidence of adverse cardiovascular outcomes. TZDs also may reduce cardiovascular events by acting directly on vascular smooth muscle cells and by helping patients maintain normal hemoglobin levels, without the risk of hypoglycemia. Furthermore, prolonged glycemic control is expected with TZDs because of their effects on beta-cell rejuvenation, a function unique to this class. TZDs can be used safely in renally impaired patients with diabetes, and hepatotoxicity has not been a problem with second-generation TZDs, making these agents both safe and effective in the treatment of type 2 diabetes.