In vivo insulin action and muscle glycogen synthase activity in type 2 (non-insulin-dependent) diabetes mellitus: effects of diet treatment.
Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110 +/- 11 to 183 +/- 23 mg.m-2.min-1 (p less than 0.03); control subjects: 219 +/- 23 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetes). Non-oxidative glucose disposal increased from 74 +/- 17 to 138 +/- 19 mg.m-2.min-1 (p less than 0.03), control subjects: 159 +/- 22 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58 +/- 0.54 to 3.35 +/- 0.23 mumol.l-1.min-1 (p less than 0.05), control subjects: 2.99 +/- 0.86 mumol.l-1.min-1 (p = NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r = 0.97, p less than 0.001), reductions in serum fructosamine (r = 0.77, p less than 0.05), and weight loss (r = 0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bak
J F
JF
Medical Endocrinological Department C, Aarhus Amtssygehus, Denmark.
Møller
N
N
Schmitz
O
O
Saaek
A
A
Pedersen
O
O
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002151:Calorimetry; D003920:Diabetes Mellitus / Q000201:enzymology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003927:Diet, Diabetic; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D019270:Fructosamine; D006006:Glycogen Synthase / Q000378:metabolism*; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009765:Obesity; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006595:Hexosamines; D007328:Insulin; D019270:Fructosamine; D006006:Glycogen Synthase; D011972:Receptor, Insulin