Restoration of early insulin secretion after a meal in type 2 diabetes: effects on lipid and glucose metabolism

• Published in: European journal of clinical investigation 2004-07, Vol.34 (7), p.490-497
• Main Authors: Dimitriadis, G., Boutati, E., Lambadiari, V., Mitrou, P., Maratou, E., Brunel, P., Raptis, S. A.
• Format: Article
• Language: English
• Subjects: Adipose tissue; Biological and medical sciences; blood flow; Blood Glucose - metabolism; Cyclohexanes - therapeutic use; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; General aspects; Humans; Hypoglycemic Agents - therapeutic use; Insulin - metabolism; Insulin Secretion; Lipid Metabolism; meal; Medical sciences; Middle Aged; Nateglinide; non-esterified fatty acids; Phenylalanine - analogs & derivatives; Phenylalanine - therapeutic use; Postprandial Period
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01377.x

Background  In type 2 diabetes (T2D) insulin secretion after a meal is delayed; this may have an impact on the development of hyperglycaemia and hyperlipidaemia. Design  To investigate this, a meal was given to 15 T2D (age 52 ± 2 years, BMI 25 ± 0·8 kg m−2) on three different occasions: (1) without treatment, (2) after 120 mg of nateglinide before the meal (acute treatment), and (3) after 3 months of nateglinide (120 mg t.i.d., chronic treatment). Fifteen healthy subjects (CON, age 48 ± 2 years, BMI 24 ± 0·5 kg m−2) were also studied. Blood was withdrawn for 360 min from veins draining the anterior abdominal subcutaneous adipose tissue (AD) and from an arterialized hand vein. Blood flow (BF) in AD was measured with 133Xe. Lipoprotein lipase activity (LPL) was calculated as the triacylglycerol (TAG) flux across AD, and hormone‐sensitive lipase (HSL) as the glycerol flux minus LPL. Results  (1) In T2D the increase in prandial insulin secretion was delayed; postprandial nonesterified fatty acid (NEFA) and TAG levels in blood were increased, while BF, LPL and TAG clearance were blunted vs. CON. (2) Acute or chronic nateglinide treatment induced a prompt increase in prandial insulin secretion, resulting in a decrease in blood glucose and NEFA levels owing to suppression of HSL, while BF, LPL and TAG clearance remained suppressed. Conclusions  In T2D, restoration of early phase insulin secretion improved postprandial hyperglycaemia and suppressed endogenous lipolysis, resulting in suppression of NEFA levels. These results suggest that in nonobese T2D, metabolic defects may result, to a large extent, from the delay in prandial insulin secretion.