Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient.

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.

Effect of exercise training on serum leptin levels in type 2 diabetic patients.

To evaluate the effect of exercise training on serum leptin levels 50 sedentary subjects with type 2 diabetes were enrolled in either 6 weeks of aerobic exercise training with diet therapy (n = 23) or diet therapy alone (n = 27). The training program consisted of walking and cycle ergometer exercise for 1 hour at least 5 times per week, with the intensity of exercise maintained at 50% of maximum oxygen uptake. Serum leptin levels decreased significantly in the exercise training (TR) group (7.2 +/- 3.6 to 4.6 +/- 2.5 ng/mL, P <.05), but not in the sedentary (SED) group (6.9 +/- 3.4 to 5.6 +/- 2.9 ng/mL). Leptin levels standardized for percentage body fat (dividing serum leptin level by percentage body fat) after treatment were lower in the TR subjects compared with the SED subjects. Body weight and percentage body fat decreased in all patients; however, no significant changes were observed in either group. Fasting concentrations of plasma insulin and cortisol and the urinary excretion of 17-hydroxycorticosteroid (17-OHCS) did not differ between the groups either before or after treatment. Fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) improved significantly in both groups, although no significant differences were observed between the groups either before or after treatment. Ventilatory threshold increased significantly in the exercise training subjects. This study demonstrates that exercise training in type 2 diabetic subjects reduces serum leptin levels independent of changes in body fat mass, insulin, or glucocorticoids.

Type IV phosphodiesterase inhibitor suppresses insulin-dependent myocardial glucose uptake.

1. Phosphodiesterase (PDE) IV has been localized at cardiomyocytes and the coronary vasculature and modulates cAMP, but the effect of PDE IV on myocardial glucose uptake has not been demonstrated. 2. Glucose uptake in rat isolated hearts treated with the PDE IV inhibitor rolipram was measured by [31P] nuclear magnetic resonance spectroscopy. 3. Under non-stimulating conditions, glucose uptake was not significantly different between control and rolipram (1 micromol/L)-treated rat hearts, whereas enhanced uptake in insulin-stimulated conditions was significantly attenuated by rolipram. 4. Phosphodiesterase IV inhibitor negatively affects insulin-dependent myocardial glucose uptake.

Clinical efficacy of insulin-like growth factor-1 in a patient with autoantibodies to insulin receptors: a case report.

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance. Treatments including steroids, cyclophosphamide, plasmapheresis, or insulin-like growth factor-1 (IGF-1) are chosen according to severity of insulin resistance. We describe a patient with type B insulin resistance syndrome who was treated successfully with human recombinant (hr) IGF-1, although this treatment provoked a severe allergic reaction. An elderly man with impaired glucose tolerance and unpredictable hypoglycemic episodes which were gradually worsening increased in hemoglobin (Hb)A1c concentration from 6.5 to 13.4%. His fasting and postprandial hyperglycemia were associated with severe hyperinsulinemia. The patient was diagnosed with type B insulin-resistance syndrome by the presence of anti-insulin receptor antibodies. Double-filtration plasmapheresis, plasma exchange, and immunosuppressive therapy with cyclophosphamide and cyclosporin all failed to suppress anti-insulin receptor antibodies more than transiently. When we attempted the treatment by daily administration of hrIGF-1, fasting and postprandial plasma glucose concentrations became normal and HbA1c levels decreased to 7.1% over 2 months, until on one occasion administration resulted in anaphylaxis. After the patient became stable, desensitization therapy was performed successfully, and hrIGF-1 could be administered again with the plasma glucose returning. We concluded that IGF-1 therapy was an effective treatment choice for type B insulin-resistance syndrome in cases whose plasma exchange and immunosuppressive therapy have failed.

Resistance training improves insulin sensitivity in NIDDM subjects without altering maximal oxygen uptake.

OBJECTIVE: To examine the effect of resistance training on insulin sensitivity in nonobese NIDDM patients. RESEARCH DESIGN AND METHODS: Previously sedentary nonobese NIDDM patients were enrolled in a resistance training group (RT; n = 9) or used as sedentary control subjects (SED; n = 8). SED subjects did not perform exercise training because of orthopedic disorders. The training program consisted of two sets of nine exercises with 10-20 repetitions. Subjects trained five times a week for 4-6 weeks. Insulin sensitivity, as assessed by the hyper-insulinemic-euglycemic clamp technique, HbAJc, and body composition, was measured before and after the training period. Maximal oxygen uptake (VO2max) and quadriceps strength were measured in the RT group. RESULTS: The two groups did not differ significantly on any variables before participation in the program. The glucose disposal rate during the hyperinsulinemic-euglycemic clamp increased 48% in the RT group (6.85 +/- 1.86 to 10.12 +/- 3.15 mg.kg-1 lean body mass.min-1; P < 0.05), but remained unchanged in the SED group (5.95 +/- 1.63 to 6.36 +/- 1.61 mg.kg-1 lean body mass.min-1). There was no significant change in body composition in either group. In the RT group, a 16% increase in quadriceps strength (191.1 +/- 45.8 to 216.9 +/- 42.8 Nm; P < 0.05) but no significant change (27.6 +/- 5.0 to 28.6 +/- 6.5 ml.kg-1.min-1) in VO2max was observed. CONCLUSIONS: Moderate-intensity, high-volume resistance training improves insulin sensitivity in nonobese NIDDM without altering VO2max.

Troglitazone ameliorates insulin resistance in a diabetic patient with Prader-Willi syndrome.

We report a patient with Prader-Willi syndrome (PWS) complicated by diabetes mellitus. PWS is a genetic disorder characterized by obesity, mental retardation and hypogonadism. Glucose intolerance in this syndrome is thought to be secondary to insulin resistance associated with morbid obesity. Therapy was directed primarily at decreasing insulin resistance and thereby improving glucose intolerance by the administration of troglitazone, which increases insulin sensitivity. Changes in glucose disposal rate assessed by euglycemic hyperinsulinemic clamp test were measured, as well as glucose and insulin responses to a 75 g-OGTT before and after troglitazone therapy. Glucose disposal rate increased by 36% and plasma glucose responses to 75 g-OGTT decreased by about 50% during 12 weeks of troglitazone therapy despite slight weight gain. Thus, troglitazone has beneficial effects on glycemic control by improving insulin sensitivity in patients with PWS complicated by diabetes mellitus.

Promotion of rectal absorption of sodium ampicillin by disodium glycyrrhetinic acid 3 beta-O-monohemiphthalate in rats.

The promotional effect on rectal absorption of sodium ampicillin (ABPC) by the glycyrrhetinic acid derivative disodium glycyrrhetinic acid 3 beta-O-monohemiphthalate (GA MHPh) was studied in rats and compared with those of sodium caprate (CAP) and sodium glycocholate (GLY). Duration of the promotive effect of GA MHPh was also studied. Rectal absorption of ABPC was significantly enhanced by addition of GA MHPh at an optimum concentration of about 1.5%. The plasma maximum concentration of ABPC was 78.71 micrograms/ml 10 min after its rectal administration at 100 mg/kg with 1.5% GA MHPh. The bioavailability of ABPC with and without 1.5% GA MHPh was 82.12% and 3.92%, respectively. Thus, absorption of ABPC in the presence of 1.5% GA MHPh was about 21 times that of ABPC alone. GA MHPh was more effective as an absorption promoter than either CAP or GLY. Its promoting action on the mucosal membrane was apparent immediately, reached a maximum at 5 min and remained for at least 20 min after rectal administration of the solution. It is therefore suggested that GA MHPh is a very useful promoter absorption of the hydrophilic drug ABPC when administered rectally.