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Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):325-30. Epub 2003 Dec 18.
3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes.

Vehkavaara S, Yki-Jarvinen H.

Department of Medicine, Division of Diabetes, University of Helsinki,Helsinki, Finland.

OBJECTIVE: To determine long-term effects of insulin glargine on vascular function in patients with type 2 diabetes. METHODS AND RESULTS: A total of 49 in vivo endothelial function tests, intrabrachial artery infusions of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasoactive agents, were performed in 11 patients with type 2 diabetes (age: 59+/-2 years; BMI: 29.7+/-0.9 kg/m2; fasting plasma glucose: 226+/-14 mg/dL) and 16 matched normal subjects. The tests in the type 2 diabetic patients were performed before and after 6 months and 3.5 years of combination therapy with insulin glargine and metformin. A control group of type 2 diabetic patients not treated with insulin was studied twice at 6-month intervals. Before treatment, blood flow during infusions of low and high doses of ACh were significantly lower in the type 2 diabetic patients than in the normal subjects (P=0.021 for ANOVA). In the patients with type 2 diabetes, blood flow during infusion of the low dose of ACh averaged 7.1+/-0.8 mL/dL per minute at baseline, 8.8+/-1.0 mL/dL per minute at 6 months (NS), and then increased compared with baseline by 87+/-29% to 11.6+/-1.4 mL/dL per minute at 3.5 years (P<0.02 versus baseline). Blood flow during infusion of the high dose of ACh increased from 8.8+/-0.9 at baseline to 13.0+/-1.9 mL/dL per minute at 6 months (P<0.05) and by 86+/-25% to 14.7+/-1.6 mL/dL per minute at 3.5 years (P<0.01 versus baseline), which was not different from normal subjects. Blood flow during infusion of low (blood flow at 0 months: 7.7+/-0.5; at 6 months: 9.9+/-0.6; P<0.01 for 6 versus 0 months; and 3.5 years: 11.6+/-1.1 mL/dL per minute; P<0.02 for 3.5 years versus 0 months) and high (blood flow at 0 months: 10.7+/-0.9; 6 months: 13.4+/-1.0; P<0.05 for 6 versus 0 months; and 3.5 years: 16.6+/-1.5 mL/dL per minute; P<0.05 for 3.5 years versus 0 months) doses of SNP also increased significantly during insulin therapy. CONCLUSIONS: We conclude that insulin glargine therapy improves endothelium-dependent and endothelium-independent vasodilatation. These data support the idea that long-term insulin therapy has beneficial rather than harmful effects on vascular function in type 2 diabetes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14684428&dopt=Abstract [PubMed - in process]

iol.it

AIM: Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). METHODS: Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or FHD (n=6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. RESULTS: In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/- 0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p<0.01), however, was observed for the 'decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. CONCLUSIONS: Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and 'prediabetic' obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14686957&dopt=Abstract [PubMed - in process]

umn.edu

OBJECTIVES: To determine the prevalence and predictors of antidiabetic medication use over a 10-year period in a general population of African-American and white community-dwelling elderly. DESIGN: Survey. SETTING: Five adjacent counties (one urban and four rural) in the Piedmont area of North Carolina. PARTICIPANTS: Those aged 65 and older present at the baseline (n=4,136), second (n=3,234), third (n=2,508), and fourth (n=1,633) in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: The use of six discrete categories of antidiabetic medications (insulin, first-generation oral sulfonylureas, second-generation oral sulfonylureas, metformin, oral combination therapy, and insulin combination therapy) was determined. Multivariate analyses, using weighted data adjusted for sampling design, were conducted to assess the association between antidiabetic medication use and race and other sociodemographic, health-status, and access-to-healthcare factors at baseline and 10 years later. RESULTS: Antidiabetic medications were taken by 21.4% of the population at baseline; this increased to 28.1% at the 10-year follow-up (P<.001). Insulin was the most commonly used drug at baseline (7.9%). The use of second-generation sulfonylureas increased, and use of first-generation sulfonylureas decreased over the 10-year time period. Combination antidiabetic therapy and metformin use was infrequent throughout the study. Multivariate analyses revealed that, at baseline, African Americans were nearly twice as likely (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.46-2.54) to receive any antidiabetic medication as their white counterparts. Other significant (P<.05) factors were hypertension (AOR=1.38, 95% CI=1.03-1.84), stroke (AOR=1.98, 95% CI=1.43-2.73), one or more mobility difficulties (AOR=1.29, 95% CI=1.01-1.66), continuity of care (AOR=1.74, 95% CI=1.20-2.54), and multiple doctor visits (1-4 visits, AOR=1.69, 95% CI=1.08-2.65; >/=5 visits, AOR=3.15, 95% CI=1.95-5.07). Being underweight (AOR=0.45, 95% CI=0.30-0.67) and being cognitively impaired (AOR=0.60, 95% CI=0.41-0.87) were factors significantly (P<.05) associated with a decreased risk of antidiabetic medication use. At the 10-year follow-up, similar trends were seen associating these sociodemographic, health-status, and access-to-healthcare factors with antidiabetic medication use. CONCLUSION: Antidiabetic medication use is common and increases over time for community-dwelling elderly. Race is significantly associated with antidiabetic medication use, even after controlling for other sociodemographic, health-status, and access-to-healthcare variables.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14687353&dopt=Abstract

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