Altering source or amount of dietary carbohydrate has acute and chronic effects on postprandial glucose and triglycerides in type 2 diabetes: Canadian trial of Carbohydrates in Diabetes (CCD).

BACKGROUND AND AIMS: Nutrition recommendations for type 2 diabetes (T2DM) are partly guided by the postprandial responses elicited by diets varying in carbohydrate (CHO). We aimed to explore whether long-term changes in postprandial responses on low-glycemic-index (GI) or low-CHO diets were due to acute or chronic effects in T2DM. METHODS AND RESULTS: Subjects with diet-alone-treated T2DM were randomly assigned to high-CHO/high-GI (H), high-CHO/low-GI (L), or low-CHO/high-monounsaturated-fat (M) diets for 12-months. At week-0 (Baseline) postprandial responses after H-meals (55% CHO, GI = 61) were measured from 0800 h to 1600 h. After 12 mo subjects were randomly assigned to H-meals or study diet meals (L, 57% CHO, GI = 50; M, 44% CHO, GI = 61). This yielded 5 groups: H diet with H-meals (HH, n = 34); L diet with H- (LH, n = 17) or L-meals (LL, n = 16); and M diet with H- (MH, n = 18) or M meals (MM, n = 19). Postprandial glucose fluctuations were lower in LL than all other groups (p < 0.001). Changes in postprandial-triglycerides differed among groups (p < 0.001). After 12 mo in HH and MM both fasting- and postprandial-triglycerides were similar to Baseline while in MH postprandial-triglycerides were significantly higher than at Baseline (p = 0.028). In LH, triglycerides were consistently (0.18-0.34 mmol/L) higher than Baseline throughout the day, while in LL the difference from Baseline varied across the day from 0.04 to 0.36 mmol/L (p < 0.001). CONCLUSION: Low-GI and low-CHO diets have both acute and chronic effects on postprandial glucose and triglycerides in T2DM subjects. Thus, the composition of the acute test-meal and the habitual diet should be considered when interpreting the nutritional implications of different postprandial responses.

Low glycaemic index diet and disposition index in type 2 diabetes (the Canadian trial of carbohydrates in diabetes): a randomised controlled trial.

AIMS/HYPOTHESIS: We recently found that oral glucose tolerance over 1 year in type 2 diabetic patients declined to a significantly lesser degree on a low-glycaemic-index than on a reduced-carbohydrate diet. Here, we examined whether that finding was associated with an improvement in disposition index, an index of beta cell function defined as the product of insulin sensitivity and insulin secretion. Since this is a report of secondary analysis on a previously published trial, the results should be considered as hypothesis-generating. METHODS: Type 2 diabetic patients treated by diet alone (n = 162) were randomised by computer to high-carbohydrate/high-glycaemic index (High-GI, n = 52), high-carbohydrate/low-glycaemic index (Low-GI, n = 56) or low-carbohydrate/high-monounsaturated-fat (Low-CHO, n = 54) diets for 1 year in a multi-centre, parallel-design clinical trial conducted at University teaching hospitals. At baseline and at 3, 6 and 12 months participants underwent 75 g OGTTs; 27 participants dropped out or were excluded. Indices of insulin sensitivity, insulin secretion and disposition index, derived from the OGTT, were compared among diets. Those assessing the outcomes were blinded to group assignment. RESULTS: Neither muscle insulin sensitivity index nor insulinogenic index differed significantly among diets. However, a significant time x diet interaction existed for disposition index (muscle insulin sensitivity index x insulinogenic index) (p = 0.036). After 3 months, disposition index tended to be higher on Low-CHO than on Low-GI diets, namely by 0.07 h(-1) (95% CI -0.04, 0.18). However, by 12 months this reversed and disposition index became higher on Low-GI than on Low-CHO, namely by 0.12 h(-1) (0.01, 0.23; p < 0.05, baseline disposition index 0.23 h(-1)). There were no important adverse effects associated with the treatments. CONCLUSIONS/INTERPRETATION: These results suggest that, in patients with type 2 diabetes on diet alone, a Low-GI diet for 1 year increases disposition index, an index of beta cell function, compared with a Low-CHO diet.

Quality of life in type 2 diabetes patients under intensive multitherapy.

AIM: To assess the impact of an intensive multitherapy (IMT) on perceived quality of life (QOL), attitudes, knowledge and diabetes self-management in patients with poorly controlled type 2 diabetes. METHODS: A 12-month randomized trial was conducted in 72 patients with type 2 diabetes, HbA1c>or=8%, blood pressure (BP)>130/80 mmHg and dyslipidemia. Subjects were assigned to the IMT or control group, each n=36. IMT consisted in monthly visits including clinical and biochemical assessment, education sessions on diet, physical exercise, medical management of diabetes and associated diseases and adjustments in medication. Control patients were under the care of their physicians. We developed and validated a diabetes-specific questionnaire assessing QOL, attitudes, knowledge, diabetes self-management and socio-demographic data for this study. Outcomes were measured at 0, 6 and 12 months. RESULTS: Subjects were 54.8+/-8.1 years old (duration of diabetes: 10.3+/-7.2 years). At baseline, questionnaires showed no difference in QOL between groups. At 12 months, QOL improved significantly in the IMT group when compared to controls (+13.2+/-10.3/+5.6+/-13.2%, P=0.003), particularly with respect to the satisfaction scale (+25.3+/-13.9/+5.4+/-21.7%, P<0.001). QOL was not affected by complications or hypoglycaemic episodes. QOL scores improved in IMT subjects who began insulin therapy during the trial. Attitude scores, in the high normal range at baseline, did not change. Knowledge (+18.2+/-26.3/+8.9+/-30.4%, P=0.047) and diabetes self-management (+22.6+/-35.3/+6.8+/-20.1%, P<0.001) improved. CONCLUSIONS: In poorly controlled subjects, QOL improved statistically despite the inherent constraints imposed by IMT.

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner.

AIMS: Insulin is a potent stimulator of adipose tissue lipoprotein lipase (LPL). Logically, the postprandial period is therefore a privileged time of the day for the regulation of LPL by insulin in this tissue. It is not clear to what extent a defect such as insulin resistance could affect this regulation and contribute to postprandial, as well as fasting, hypertriglyceridaemia. The aim of the present protocol was to study the relationship between insulin resistance and LPL in adipose tissue and in plasma, in the particular context of the postprandial period. METHODS: For this study, 26 adult nondiabetic individuals (12 women and 14 men) with a wide range of whole-body insulin-mediated glucose uptake (as assessed with an insulin suppression test) were studied. An abdominal subcutaneous fat biopsy on one occasion, and post-heparin plasma on another occasion, were obtained 4 h into a standardized meal profile administered in the fasting state. RESULTS: Postprandial triglyceride excursions (evaluated by the incremental area under the curve during the metabolic meal profile) were inversely correlated to adipose tissue LPL mRNA levels (rho = -0.43, P < 0.03) as well as to adipose tissue LPL heparin-releasable activity (rho = -0.58, P < 0.01). Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test, a reflection of the degree of insulin resistance, were also negatively correlated to adipose tissue LPL mRNA (rho = -0.50, P < 0.02) and activity (rho = -0.56, P < 0.01). There was no correlation between plasma post-heparin LPL activity/mass and postprandial triglycerides nor with insulin resistance. CONCLUSION: Regulation of adipose tissue LPL is significantly affected in insulin-resistant individuals in the postprandial period. This presumed impaired effect of insulin on LPL postprandially could be an important contributor to the atherogenic dyslipidaemia described in insulin resistance syndrome.

Induction of cholesteryl ester transfer protein in adipose tissue and plasma of the fructose-fed hamster.

Cholesteryl ester transfer protein (CETP) plays a pivotal role in the reverse transport of cholesterol and in the remodeling of circulating lipoproteins. While plasma and adipose tissue levels of CETP are affected by a variety of metabolic conditions, the extent of the effects of dietary factors, other than high cholesterol feeding, are not well understood. To further explore this paradigm, male Golden Syrian hamsters were fed for 4 weeks with a 60%-enriched fructose diet (F) and were compared to a matched group of animals fed with a normal chow diet (N). After feeding for 4 weeks, plasma insulin concentrations were lower in animals fed fructose than in control animals (F: 3.3+/-0.8 vs N: 7.4+/-1.9 ng/mL; p<0.03), but there was no significant difference in plasma glucose concentrations between the two groups (F: 138+/-7 vs N: 148+/-10 mg/dL; p>0.05). Fructose-fed animals showed significant increases in plasma triglyceride (F: 269+/-22 vs N: 165+/-22 mg/dL; p<0.01) and plasma cholesterol (F: 150+/-10 vs N: 113+/-6 mg/dL; p<0.02) concentrations compared with control animals. Total CETP activity and immunoreactive mass were higher in the plasma of fructose-fed animals that in that of controls (F: 1036+/-70 vs N: 826+/-43 pmol/h/mL, p<0.04 and F: 24.5+/-3.1 vs N: 37.5+/-4.3 AU, p<0.02, respectively). Adipose tissue CETP mRNA levels, assessed by the very sensitive ribonuclease protection assay, were 53% higher in fructose-fed animals than in controls (F: 14.1+/-2.0 vs N: 9.2+/-1.0 AU over a rRNA control; p<0.04). Adipose tissue CETP activity and immunoreactive mass also showed a statistically significant increase in the fructose-fed hamsters compared with those fed a normal diet (p<0.04). In conclusion, fructose feeding in Syrian hamsters induces a mixed dyslipidemia. These metabolic changes are accompanied by a significant increase in CETP levels, both in plasma and in adipose tissue. This phenomenon suggests that the increase in the expression of adipose tissue CETP may be caused either by the ambient hypercholesterolemia resulting from fructose feeding or by an attenuation of a possible inhibitory effect of plasma insulin concentrations on the expression of adipose tissue CETP in this feeding paradigm.

Lipoprotein lipase steady-state mRNA levels are lower in human omental versus subcutaneous abdominal adipose tissue.

Adipose tissue synthesizes lipoprotein lipase (LPL), which helps in the postprandial clearance of triglyceride-rich lipoproteins. Because visceral adipose tissue is generally accepted as the most important metabolic tissue, we sought to verify whether there are regional differences in the expression of LPL. Samples of adipose tissue from subcutaneous and omental fat deposits were obtained from 20 adults undergoing surgery. Total adipose tissue LPL activity was measured using a conventional radioactive substrate assay. Steady-state levels of LPL mRNA were assessed using the very sensitive RNase protection assay technique with 18S ribosomal RNA as an internal control. A correlation was demonstrated between LPL activity levels in subcutaneous and omental tissue (r = .72; P < .01) and between mRNA levels at both sites (r = .47, P = .04). LPL mRNA levels were significantly lower in omental compared with subcutaneous depots (omental v subcutaneous, 1.7 +/- 0.7 v 2.1 +/- 0.7 arbitrary units [AU] over 18S, P < .05). In paired comparisons, LPL mRNA levels in omental adipose tissue were, on average, 20% +/- 7% (range, -57% to +9.0%) lower than the levels measured in subcutaneous adipose tissue (P < .05). In conclusion, these data suggest that subcutaneous adipose tissue is a reliable surrogate of the expression (activity and mRNA) of LPL in omental adipose tissue, even though omental depots express proportionally less LPL than subcutaneous depots.

Effect of acarbose on insulin sensitivity in elderly patients with diabetes.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.

Evaluation of postural stability in elderly with diabetic neuropathy.

OBJECTIVE: The objective of this study was to compare clinical and biomechanical characteristics of balance in diabetic polyneuropathic elderly patients and normal age-matched subjects. RESEARCH DESIGN AND METHODS: Fifteen elderly with distal neuropathy (DNP) and 15 healthy age-matched subjects were evaluated with the biomechanical variable COP-COM, which represents the distance between the center of pressure (COP) and the center of mass (COM). Measurements were taken in the quiet position with a double-leg stance, in eyes-open (EO) and eyes-closed (EC) conditions. Subjects were also assessed with clinical balance evaluations. RESULTS: The COP-COM variable was statistically significantly larger in the DNP group than in the healthy group in anterior-posterior (A/P) and medial-lateral (M/L) directions. Furthermore, the DNP group showed statistically significantly larger amplitudes of the COP-COM variable without vision. The severity of the neuropathy, as quantified using the Valk scoring system, was correlated with COP-COM amplitude in both directions. CONCLUSIONS: Evaluation of the postural stability of an elderly diabetic population using the COP-COM variable can detect a very small change in postural stability and could be helpful in identifying elderly with DNP at risk of falling.

The degree of hyperinsulinemia and impaired glucose tolerance predicts plasma leptin concentrations in women only: a new exploratory paradigm.

Plasma leptin has been shown to correlate positively with many indices of obesity, as well as insulin resistance. For a given body weight, the levels are higher in women than in men, but the reasons for this difference are not clear. Insulin has been shown to stimulate leptin production by adipose tissue in vivo and in vitro. Previous studies have reported that leptin levels are similar in diabetic and nondiabetic individuals. However, these studies were not performed in newly diagnosed diabetics, and other variables (such as gender) could have confounded the results. Therefore, the goal of the present cross-sectional study is to examine the effect of metabolic variables (such as glucose and insulin) on plasma leptin concentrations in men and women separately. We measured leptin levels in 48 subjects (17 with newly diagnosed type 2 diabetes mellitus, 13 with impaired glucose tolerance [IGT], and 18 normal individuals). The 3 groups were well matched for gender, age, and body mass index (BMI). When adjusted for the BMI and gender, a statistically significant gender-related difference in mean plasma leptin was observed across the 3 glucose tolerance subgroups (P < .03 by analysis of covariance [ANCOVA]). More specifically, plasma leptin levels were, on average, 44% lower in women with diabetes or IGT versus normal women (P < .02). No such between-group difference was observed in the men. In univariate analysis in the same female subgroup, plasma leptin correlated positively with fasting insulin (rs = +.43, P < .06) and negatively with 2-hour post-75-g glucose load plasma glucose concentration (rs = -.54, P < .02). In a multiple regression model controlling for the BMI in the female subgroup, circulating insulin and glucose concentrations 2 hours after the 75-g glucose load were good predictors of fasting plasma leptin (r = +.38, P = .02 and r = -.70, P < .001, respectively). Leptin levels in women appear to be influenced independently and to an important degree by ambient plasma glucose and plasma insulin concentrations. These findings suggest that the synthesis of leptin by adipose tissue is more susceptible to in vivo regulation by insulin and glucose in women than in men. Plasma leptin concentrations were also lower in women with IGT or type 2 diabetes versus normal women, suggesting that fasting and/or postprandial hyperglycemia interferes with the stimulatory effect of plasma insulin on the synthesis of leptin by adipose tissue in women only.

Pigmented adrenal hyperplasia with myelolipomatous changes and bilateral testicular enlargement in an untreated man with 21-hydroxylase deficiency.

OBJECTIVE: To report the occurrence of a giant left adrenal tumor and bilateral testicular masses (adenomatous hyperplasia of Leydig cells) in a young man with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. METHODS: The clinical, radiologic, endocrinologic, and pathologic features of this case are correlated with the findings in the literature. RESULTS: The interesting elements in this case are the rare pathologic features of the left adrenal lesion (pigmented adrenal hyperplasia with myelolipomatous changes) and the association with the infrequent testicular adrenal rest tumors. The absence of enlargement of the right adrenal gland was unexplained. CONCLUSION: The presence of these two rare complications seemed to be associated with poor adherence to medical treatment recommendations for congenital adrenal hyperplasia.

Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.

The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.

Preoperative localization of parathyroid lesions in hyperparathyroidism: relationship between technetium-99m-MIBI uptake and oxyphil cell content.

UNLABELLED: The aim of this study was to assess the relationship between parathyroid oxyphil cell content and early or late phases of uptake of 99mTc-MIBI, a radioisotope preferentially retained in mitochondria-rich cells. METHODS: This study is a retrospective, single-blind analysis of all double-phase 99mTc-MIBI parathyroid scintigraphy studies performed before surgery in our institution between 1990 and 1995. A total of 18 parathyroid lesions in 14 patients were reviewed. This sample included 11 cases of primary hyperparathyroidism (8 adenomas, 1 adenocarcinoma and 2 hyperplasias) and 3 cases of tertiary hyperparathyroidism secondary to chronic renal failure. RESULTS: Uptake of 99mTc-MIBI in the early phase of scintigraphy was associated with larger parathyroid lesions (1.61 +/- 1.61 ml versus 0.33 +/- 0.27 ml; p < 0.02) and higher serum calcium levels (3.00 +/- 0.41 mM versus 2.67 +/- 0.14 mM; p < 0.02). More importantly, we found that a parathyroid oxyphil cell content greater than 25% was more often associated with a positive uptake of 99mTc-MIBI in the late phase of the test (positive late uptake in 78% of lesions with a high oxyphil cell content versus 33% in lesions with an oxyphil cell content between 1% and 25% and 0% in lesions with no oxyphil cells; p < 0.04). CONCLUSION: These findings suggest that the late retention of 99mTc-MIBI in double-phase scintigraphy is related to parathyroid oxyphil cell content.

Reduction of capillary permeability in the fructose-induced hypertensive rat.

Impaired insulin transcapillary transport and the subsequent decrease in insulin delivery to target organs have been suggested to play a role in insulin resistance. These defects were studied in fructose-fed rats, an animal model with insulin resistance. For this study, male Sprague-Dawley rats were fed with either a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8 weeks. Capillary permeability to albumin was assessed at the end of each dietary period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in different organs. Unanesthetized animals were injected with Evans blue dye (20 mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by formamide from selected organs collected after exsanguination. As expected, rats had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F, 149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a 56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8 weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/- 3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05). Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8 microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin (N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P < .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F, 80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is accompanied by a significant and selective reduction of Evans blue leakage primarily in skeletal muscle and liver, and transiently in the skin and aorta, consistent with a role for decreased tissue insulin delivery in insulin resistance.

Evidence that insulin can directly inhibit hepatic glucose production.

In order to evaluate the role of portal insulin in the modulation of hepatic glucose production (HGP), measurements of plasma glucose and insulin concentrations and both HGP and peripheral glucose disappearance rates were made following an infusion of a dose of tolbutamide (0.74 mg x m(-2) x min[-1]) in healthy volunteers that does not result in an increase in peripheral vein insulin concentrations or metabolic clearance rate of glucose. The results showed that the infusion of such a dose of tolbutamide was associated with a significant and rapid decline in both HGP (from 9.0 +/- 0.5 to 7.7 +/- 0.5 micromol x kg(-1) x min(-1) or delta = -13.8 +/- 4.5%; p < 0.001 compared to saline) and plasma glucose concentration (from 5.1 +/- 0.2 to 4.4 +/- 0.1 mmol/l or delta = -13.0 +/- 2.1%; p < 0.01 compared to saline). Since neither HGP nor fasting glucose fell when tolbutamide-stimulated insulin secretion was inhibited by the concurrent administration of somatostatin, it indicated that tolbutamide by itself, does not directly inhibit HGP. Finally, HGP fell by 26.3 +/- 6.0% at 10 min after a dose of tolbutamide that elevated both peripheral and portal insulin concentrations, at a time when HGP had barely increased (delta = +6.9 +/- 5.3%). The difference in the magnitude of the two responses was statistically significant (p < 0.03), providing further support for the view that insulin can directly inhibit HGP, independent of any change in flow of substrates from periphery to liver.

Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase.

The relationship between insulin-mediated glucose disposal and fasting insulin and triglyceride (TG) concentrations, plasma post-heparin lipoprotein lipase (PH-LPL) activity and mass, and adipose tissue LPL activity, mass, and mRNA content was defined in 19 non-diabetic men. Insulin-mediated glucose uptake [as assessed by determining the steady-state plasma glucose (SSPG) concentration during a continuous infusion of somatostatin, insulin, and glucose] was significantly correlated with fasting TG concentration (r = 0.54, p < 0.02), plasma PH-LPL activity (r = -0.52, p < 0.03) and mass (r = -0.49, p < 0.03), and adipose tissue LPL mRNA content (r = -0.68, p < 0.001). Comparable relationships were also seen when fasting insulin concentration was substituted for SSPG. Although adipose tissue LPL and mass correlated with each other (r = 0.76, p < 0.001) in a fasting state, they were not related to any other variable measured. Using in vivo and molecular biology techniques, these data demonstrate that the more insulin resistant an individual, the lower the level of plasma PH-LPL activity and mass, and the higher the plasma TG concentration. Since lower concentrations of adipose tissue mRNA were also directly correlated with plasma PH-LPL mass (r = 0.57, p < 0.01), and inversely with plasma TG concentration (r = -0.68, p < 0.001) as well as SSPG (r = -0.68, p < 0.001), it can be postulated that the relationship between insulin resistance and LPL activity and plasma TG concentration is associated with the inability of insulin to stimulate the transcription or to increase the intracellular mRNA stability of adipose tissue LPL in insulin resistant individuals.