The visceral adiposity syndrome in Japanese-American men.

Japanese-Americans have an increased prevalence of non-insulin-dependent diabetes mellitus and coronary heart disease when compared to native Japanese. This increase has been associated with fasting hyperinsulinemia, hypertriglyceridemia, and low plasma levels of high-density lipoprotein (HDL) cholesterol. The purpose of this study was to examine the relationship of both visceral adiposity and insulin resistance to this metabolic syndrome and to the presence of a predominance of small, dense low-density lipoprotein (LDL) particles (LDL subclass phenotype B) that has been associated with increased atherogenic risk. Six Japanese-American men with non-insulin-dependent diabetes, each receiving an oral sulfonylurea, were selected. One or 2 nondiabetic Japanese-American men, matched by age and body mass index, were selected for each diabetic subject, giving a total of 9 nondiabetic men. Diabetic subjects had significantly higher fasting plasma glucose (p=0.0007) and lower insulin sensitivity (SI, p=0.018) using the minimal model technique than nondiabetic subjects matched for body mass index. Six men (2 with diabetes) had LDL phenotype A and 8 (4 with diabetes) had phenotype B. One nondiabetic subject had an intermediate low-density lipoprotein pattern. Significantly greater amounts of intra-abdominal fat (p=0.045) measured by computed tomography were found in the men with phenotype B while fasting insulin (p=0.070) and triglycerides (p=0.051) tended to be higher. free fatty acids (r=0.677), LDL density (relative flotation rate, r=-0.803), and plasma HDL-cholesterol (r=-0.717). SI was significantly correlated only with plasma free fatty acids (r=-0.546) and tended to be correlated with hepatic lipase activity (r=-0.512, p=0.061). In conclusion, these observations indicate that in non-obese Japanese-American men, the metabolic features of the so-called insulin resistance syndrome, including LDL phenotype B, are more strongly correlated with visceral adiposity than with SI. It may therefore be more appropriate to call this the visceral adiposity syndrome. Although questions concerning mechanisms still remain, we postulate that visceral adiposity plays a central role in the development of many of the metabolic abnormalities, including LDL subclass phenotype B, that occur in this metabolic syndrome.

Effect of heparin on insulin-glucose interactions measured by the minimal model technique: implications for reproducibility using this method.

The minimal model technique permits investigation of glucose and insulin interactions during a frequently sampled intravenous glucose tolerance test (FSIGT). The model allows measurement of several important variables including insulin sensitivity (SI), glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI). In addition, from the FSIGT, first-phase insulin secretion (AIRglucose) and the glucose disappearance constant (Kg) can be estimated. The estimates obtained using the minimal model technique could be of importance in understanding potential relationships between carbohydrate and lipid metabolism. In studying lipoprotein lipase (LPL) activity and mass as one of the elements of lipid metabolism, heparin administration is necessary. However, the effect of administration of this agent on factors important in carbohydrate metabolism has not been fully elucidated. Therefore, to assess the effect of heparin on insulin-glucose interactions, we performed paired studies in which subjects randomly underwent FSIGT studies 20 minutes following bolus injections of heparin or saline. None of the measured parameters was influenced by heparin administration just before the FSIGT. Since these estimates were not affected by heparin administration, these studies also permitted assessment of the coefficient of variation of replicate analysis for all values generated using the minimal model technique. The coefficients of variation of replicate analysis calculated from these two studies were 16.9% for SI, 16.6% for SG, 18.3% for GEZI, 20.6% for AIRglucose, and 14.5% for Kg. These results suggest that heparin can be administered as part of a procedure that would allow concurrent assessment of various aspects of both carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Lambda light chain myeloma with pleural involvement.

A case is reported of lambda light chain multiple myeloma complicated by a myelomatous pleural effusion. Pleural effusions are uncommon in multiple myeloma, and most are secondary to nonmalignant causes. The clinical characteristics, natural history and pathophysiology of myelomatous pleural effusions are reviewed.

Amount and speed of fast axonal transport in diabetes.

Abnormalities in axonal transport have been observed in human and experimental diabetes and may be related to the pathogenesis of diabetic neuropathy. Axonal transport has previously been evaluated by indirect methods. In this study, direct-measurement techniques were applied (with computer-enhanced video-recorded images) for the first time to evaluate intra-axonal organelle speed and frequency (the amount of organelle traffic) in both the anterograde fast component (AFC) and retrograde fast component (RFC) of axonal transport in diabetic nerve. Sciatic nerve and dorsal and ventral nerve roots were studied in the animal model of insulin-dependent diabetes (BB/Wistar rat) and sciatic nerve in the non-insulin-dependent (streptozocin-induced) model of diabetes (STZ-D rat). STZ-D rats were studied at 1 mo, and BB/Wistar rats were studied at 1 and 2 mo of diabetes duration. Statistically significant decreases in peripheral axon organelle speed were found only for RFC at 1 mo of diabetes in both the BB/Wistar (8.1%) and STZ-D (5.4%) rats. The difference was no longer significant in BB/Wistar rats at 2 mo of diabetes. This recovery suggests that the underlying abnormality is reversible. No differences were seen in AFC of any axons, and the only other difference seen was a 5.1% decrement in RFC at 2 mo in the ventral roots. No significant difference was observed in any group for organelle frequencies. Other factors should be considered to explain the decrease in materials transported in accumulation studies. The transient deficits in RFC speed observed remain of undetermined significance in the pathogenesis of diabetic neuropathy.

Pathophysiology of hyperlipidemia in diabetes mellitus.

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.