Therapeutic perspectives in hyperlipidemic patients with diabetes mellitus

Abstract

Reprint requests: Abhimanyu Garg, MBBS, MD, Assistant Professor of Internal Medicine and Clinical Nutrition, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9052 Supported in part by the Veterans Administration, by grants (HL-29252, MOl-RROOW from the National Institutes of Health, by the Southwestern Medical Foundation, and by the Moss Heart Foundation of Dallas, Texas. Coronary heart disease (CHD) remains the leading cause of death in patients with both Type I, insulin-dependent diabetes mellitus (IDDM), as well as for patients with Type II, noninsulin-dependent diabetes mellitus (NIDDM). Patients with diabetes mellitus have a high frequency of dyslipidemia, which, along with hyperglycemia, hypertension, and obesity (particularly in NIDDM), may be an important contributing factor to accelerated atherosclerosis.’ Although the information available on the relative importance of various CHD risk factors in patients with diabetes mellitus is limited, it appears that hypertension and nephropathy may be the major risk factors in IDDM,*s3 whereas dyslipidemia seems to be the most important risk factor in NIDDM.Since the presence of multiple risk factors may increase the overall risk for CHD in an additive or perhaps a synergistic manner, therapeutic strategies should put equal emphasis on controlling hyperglycemia, dyslipidemia, and hypertension. Most IDDM patients who maintain good glycemic control have normal levels of lipids and lipoproteins; some may even have subnormal levels of VLDL and LDL, and increased levels of HDL-cholesterol.7~8 However, marked hypertriglyceridemia with chylomicronemia may be observed in some patients with poor glycemic control. The dyslipidemia in most of these patients may simply respond to intensive insulin therapy8 and, therefore, hypolipidemic drugs may not be justified. It has been noted, however, that IDDM patients with microalbuminuria or early incipient nephropathy may have relatively higher levels of plasma triglycerides, VLDL-cholesterol, LDL-cholesterol, and apolipoprotein B, and lower levels of HDL-cholesterol, than those without microalbuminuria.g*lo With progression of diabetic nephropathy, the dyslipidemia is reported to worsen. Therefore, those patients prone to develop nephropathy may deserve special attention for lowering lipids and lipoproteins. Since experience with hypolipidemic drugs is virtually nonexistant in IDDM patients, dietary therapy should be stressed to control dyslipidemia in most patients. In contrast to patients with IDDM, NIDDM patients have a high frequency of dyslipidemia. Although prevalence of dyslipidemia in NIDDM undoubtedly varies among different populations, most studies indicate a twoto three-fold increase over nondiabetic individuals.4~“*12 C ha racteristic lipoprotein abnormalities in NIDDM patients include hypertriglyceridemia, or elevated levels of VLDL and low levels of HDL.‘* Although most population studies do not document elevated levels of LDL-cholesterol in NIDDM patients, abnormalities in the metabolism as well as composition of LDL particles may make an important contribution to atherogenesis. There is increasing evidence that elevated triglyceride levels, which are consistently associated with an elevated VLDL-cholesterol, appear to be an independent risk factor in NIDDM patients.5,6’” Therefore, the therapeutic target in NIDDM patients should be non HDL-cholesterol, which includes both VLDL and LDL, and not just LDL-cholesterol alone.13 Several studies indicate that the presence of diabetes mellitus in women eliminates their protection against CHD,‘* and therefore we propose that the goals of therapy may be similar for both men and women. In NIDDM patients, maximal reduction in cholesterol levels may be indicated to minimize CHD risk. The minimal goal of therapy in NIDDM patients may be a non HDLcholesterol level of less than 4.14 mmol/L (160 mgldl), the ideal goal being 3.36 mmol/L (130 mg/dl). l3 In patients with low levels of HDL-cholesterol