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Data have been accumulating on the risk of developing type 2 diabetes in patients receiving statins and on the potential adverse effects of these drugs on glycemic control in patients who already have type 2 diabetes. This article reviews data linking statin use and new-onset diabetes mellitus, the effects of statins on glycemic control in type 2 diabetes, the benefit-risk considerations of statin use and type 2 diabetes, and how these factors affect patient management.

The classification of diabetes mellitus in 2020 still starts with 2 major types, ie, type 1 and type 2, but each of these now includes a few uncommon variants. Understanding the many faces of the diabetes syndrome can make a difference in how clinicians select glucose-lowering therapy.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial tested the hypothesis that intensive glucose-lowering (with a hemoglobin A1c target of less than 6.0%) would reduce the incidence of atherosclerotic disease events and death compared with standard treatment (with a hemoglobin A1c target of 7.0% to 7.9%) in more than 10,000 patients with type 2 diabetes at high risk of cardiovascular events. The study was terminated early because more people had died in the intensive-treatment group than in the standard-treatment group (257 vs. 203). The ACCORD results should not substantially alter our usual approach to glucose-lowering, which should still be "as low as we can get it safely" while avoiding hypoglycemia, significant weight gain, complex regimens, and, perhaps, the "stress" of maintaining glycemic control, especially in patients at high risk of coronary heart disease.

Insulin is not the only hormone that regulates plasma glucose levels. Glucagon-like peptide 1 (GLP-1), produced in the small intestine, and amylin, produced by beta cells in the pancreas, also have glucose-lowering effects. Synthetic analogues of these hormones are now available for clinical use.

The 2004 update to the National Cholesterol Education Program guidelines goes farther than the 2001 version in suggesting an optional low-density lipoprotein cholesterol (LDL-C) goal of less than 70 mg/dL for patients at "very high risk." It recommends starting both diet and drug therapy in all patients at high or very high risk whose LDL-C level is above the goal level, with the goal of reducing LDL-C by 30% to 40%. These more aggressive guidelines are based on results of five clinical studies published since 2001.

The cluster of hypertriglyceridemia, hyperinsulinemia, obesity, and hypertension markedly increases the risk of coronary artery disease. Although no treatments target this syndrome specifically, treatment of each aspect of the cluster is important. Prevention—weight loss and physical activity—is key. The National Cholesterol Education Program recognizes the importance of the metabolic syndrome and has published guidelines for its diagnosis. Weight loss, physical activity, and treatment of the individual risk factors constitute the main strategies for treatment. For now, the goals and methods of treating hypertension and dyslipidemia are the same in people with the metabolic syndrome as in the general population. Thiazolidinedione drugs increase insulin sensitivity, but their use in the metabolic syndrome is only speculative at present. We recommend they be used only as indicated to treat diabetes mellitus.

Pancreas transplantation can improve quality of life for patients with type 1 diabetes by eliminating hypoglycemic and hyperglycemic episodes, the need for insulin injections, frequent self-monitoring of blood glucose levels, and dietary restrictions. Increasing evidence suggests that it may slow the progression of long-term diabetic complications. On the other hand, patients risk the adverse effects of lifelong immunosuppression.

The United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive treatment (i.e., glucose-lowering drugs, with a goal fasting blood glucose level of 108 mg/dL) decreases the microvascular complications of type 2 diabetes mellitus. We summarize the key study results and their implications for clinical management of type 2 diabetes mellitus.

The Post Coronary Artery Bypass Graft trial is an important milestone that documents the benefits of treating hypercholesterolemia in patients with severe coronary atherosclerosis w h o have had bypass surgery. In the present article, w e highlight the rationale, study design, and results of the Post-CABG study, which was recently published in the New England Journal of Medicine.

Patients with diabetes mellitus are at higher risk for complications from surgery than their nondiabetic counterparts. Evidence-based guidance on the perioperative management of diabetic patients is still very limited. Management is best guided by careful preoperative and postoperative consideration of diet, antidiabetic medication regimens, and the likelihood of specific complications of diabetes. Good postoperative glucose control reduces the risk of in-hospital death and shortens length of stay. Insulin is the mainstay of perioperative glucose management, and intensive insulin therapy (to a target blood glucose of 110 mg/dL or lower) improves a range of clinical outcomes in critically ill patients relative to less aggressive insulin strategies. There is little role for oral antidiabetic medications in the early postoperative phase.

The landmark Heart Protection Study (Lancet 2002; 360:7-22) found benefit in treating subjects at high risk of a coronary event with simvastatin 40 mg daily, regardless of baseline low-density lipoprotein cholesterol level and in all subgroups, including women and the elderly. The study found no benefit of simvastatin therapy in preventing noncardiac events (eg, dementia, osteoporotic fractures), and no negative effects, such as an increase in cancer, respiratory disease, or suicide.

To give ACE inhibitors to all diabetic patients would be premature, but these agents have clear indications in some patients.

Better understanding of diabetic nephropathy’s pathophysiology has led to fundamental changes in its management: detecting nephropathy early and intervening with rigorous glycemic control and aggressive management of hypertension may slow its progression. Dietary protein restriction may also have a role.

The prevalence of abnormal lipid and lipoprotein values was determined in 125 consecutive patients with lower-extremity arteriosclerosis obliterans, and the lipid and lipoprotein abnormalities in these patients were characterized. Only 13% of the patients had normal lipid/lipoprotein profiles. Forty-eight percent of patients had low levels of high-density lipoprotein cholesterol. High-density lipoprotein cholesterol values were lower in patients with concomitant coronary heart disease compared with those without heart disease. High-density lipoprotein cholesterol values were inversely related to weight, to triglyceride values, and to diabetes mellitus. Twenty-eight percent of patients had "desirable" total cholesterol levels (< 200 mg/dL), and 32% had low-density lipoprotein cholesterol values less than 130 mg/dL. Following National Cholesterol Education Program guidelines may be misleading in patients with documented lower-extremity atherosclerosis; therefore, complete lipid/lipoprotein profiles should be performed in these patients.

The goal of this study was to determine whether the administration of an oral combined estrogen-androgen preparation would influence the lipid and lipoprotein profile of postmenopausal women. There were no pretreatment to posttreatment differences in triglycerides, total cholesterol, or in low density lipoproteins and very low density lipoproteins. However, high density lipoprotein values decreased significantly after treatment. Although further study is warranted, these preliminary findings suggest that the potential beneficial effects of oral estrogen-androgen on sexual and psychological well-being may need to be weighed against the possible cardiovascular risks of adverse lipid changes in postmenopausal women.

Decerebrate rigidity is one of several reversible neurological abnormalities which have been observed in the setting of metabolic coma. We present the case of a patient who recovered fully from prolonged decerebrate rigidity associated with hypoglycemic coma. This case emphasizes the possibility of recovery from severe, prolonged hypoglycemia.

Several investigations have assessed the relationship between glycemic control and complications in diabetes mellitus. Key evidence is reviewed that supports the beneficial effects of "tight" blood glucose control. Pertinent animal data show that good blood glucose control is associated with less retinopathy and nephropathy and fewer congenital anomalies in offspring. Short-term studies in humans show similar trends in microvascular complications and pregnancy. Similarly, peripheral neuropathy may be lessened with lower blood glucose. Although no studies have demonstrated a reduction in atherosclerotic disease with improved glycemic control, dyslipidosis frequently improves, which should reduce the risk for coronary heart and peripheral vascular disease.

The importance of an aggressive approach to diagnosis, management, and follow-up of diabetic retinopathy cannot be overstated.

Future alternatives to traditional insulin administration include closed-loop delivery systems and islet cell transplantation.