Plasma Glucose In Type Research Articles

Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes.

GLP-1 lowers blood glucose in fasting type 2 diabetic patients. To clarify the relation of the effect of GLP-1 to obesity, blood glucose, beta-cell function, and insulin sensitivity, GLP-1 (1.2 pmol/kg.min) was infused iv for 4-6 h into 50 fasting type 2 diabetic patients with a wide range of age, body mass index, HbA1c, and fasting plasma glucose. The effectiveness of GLP-1 was evaluated by calculation of a glucose disappearance constant for each individual (Kg, linear slope of log-transformed plasma glucose), and by the lowest stable glucose level (Nadir plasma glucose) obtained during the infusion. Grouped according to fasting plasma glucose (<10, 10-15, >15 mmol/liter), Kg values were 0.45 +/- 0.03, 0.38 +/- 0.04, and 0.28 +/- 0.04%/min (P = 0.005), and Nadir plasma glucose values were 4.7 +/- 0.1 (3.9-5.9), 5.8 +/- 0.4 (4.3-8.4), and 8.7 +/- 1.4 (6.2-18.7) mmol/liter (P = 0.0003). Nonresponders were not identified. Multiple regression analysis with Kg or Nadir plasma glucose as the dependent parameter and body mass index, age, gender, diabetes duration, and significantly correlated parameters (in multiple regression for Kg: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, peak insulin, and the logarithm of beta-cell function; and for Nadir plasma glucose: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, delta glucagon decrement, F-GLP-1 total, logarithm of beta-cell function, and Kg) as independent parameters resulted in fasting plasma glucose as the only significant predictor of Kg, and fasting plasma glucose and Kg as predictors of Nadir plasma glucose. Kg and Nadir plasma glucose were neither influenced by treatment nor by neuropathy per se. In conclusion, GLP-1 lowers plasma glucose in type 2 diabetes regardless of severity, but glucose elimination is faster and obtained glycemic level lower in patients with the lower fasting plasma glucose. Not all patients can be expected to reach normoglycemia.

Glucagon-Like Peptide 1 Increases Secretory Burst Mass of Pulsatile Insulin Secretion in Patients With Type 2 Diabetes and Impaired Glucose Tolerance

The insulinotropic gut hormone glucagon-like peptide (GLP)-1 increases secretory burst mass and the amplitude of pulsatile insulin secretion in healthy volunteers without affecting burst frequency. Effects of GLP-1 on secretory mechanisms in type 2 diabetic patients and subjects with impaired glucose tolerance (IGT) known to have impaired pulsatile release of insulin have not yet been studied. Eight type 2 diabetic patients (64+/-9 years, BMI 28.9+/-7.2 kg/m2, HbA1c 7.7+/-1.3%) and eight subjects with IGT (63+/-10 years, BMI 31.7+/-6.4 kg/m2, HbA1c 5.7+/-0.4) were studied on separate occasions in the fasting state during the continued administration of exogenous GLP-1 (1.2 pmol x kg(-1) x min(-1), started at 10:00 P.M. the evening before) or placebo. For comparison, eight healthy volunteers (62+/-7 years, BMI 27.7+/-4.8 kg/m2, HbA1c 5.4+/-0.5) were studied only with placebo. Blood was sampled continuously over 60 min (roller-pump) in 1-min fractions for the measurement of plasma glucose and insulin. Pulsatile insulin secretion was characterized by deconvolution, autocorrelation, and spectral analysis and by estimating the degree of randomness (approximate entropy). In type 2 diabetic patients, exogenous GLP-1 at approximately 90 pmol/l improved plasma glucose concentrations (6.4+/-2.1 mmol/l vs. placebo 9.8+/-4.1 mmol/l, P = 0.0005) and significantly increased mean insulin burst mass (by 68%, P = 0.007) and amplitude (by 59%, P = 0.006; deconvolution analysis). In IGT subjects, burst mass was increased by 45% (P = 0.019) and amplitude by 38% (P = 0.02). By deconvolution analysis, insulin secretory burst frequency was not affected by GLP-1 in either type 2 diabetic patients (P = 0.15) or IGT subjects (P = 0.76). However, by both autocorrelation and spectral analysis, GLP-1 prolonged the period (lag time) between subsequent maxima of insulin concentrations significantly from approximately 9 to approximately 13 min in both type 2 diabetic patients and IGT subjects. Under placebo conditions, parameters of pulsatile insulin secretion were similar in normal subjects, type 2 diabetic patients, and IGT subjects based on all methodological approaches (P > 0.05). In conclusion, intravenous GLP-1 reduces plasma glucose in type 2 diabetic patients and improves the oscillatory secretion pattern by amplifying insulin secretory burst mass, whereas the oscillatory period determined by autocorrelation and spectral analysis is significantly prolonged. This was not the case for the interpulse interval determined by deconvolution. Together, these results suggest a normalization of the pulsatile pattern of insulin secretion by GLP-1, which supports the future therapeutic use of GLP-1-derived agents.

Age-related changes in postprandial plasma glucose in type 2 diabetes

Age-related changes in postprandial plasma glucose in type 2 diabetes

The Effect of Glucagon-Like Peptide I (GLP-I) on Glucose Elimination in Healthy Subjects Depends on the Pancreatic Glucoregulatory Hormones

Glucagon-like peptide I (GLP-I) decreases plasma glucose in type II diabetic patients and in healthy subjects indirectly by stimulation of insulin and inhibition of glucagon secretion, whereby the hepatic glucose production decreases. However, recent studies indicate that GLP-I may also directly influence peripheral and hepatic glucose uptake. We infused somatostatin (SS) intravenously (500 or 1,000 microgram/h) in 13 healthy subjects to suppress insulin and glucagon secretion from the endocrine pancreas, together with infusion of either GLP-I (50 pmol / kg / h) or saline intravenously. After 30 min, a 25-g intravenous glucose tolerance test (IVGTT) was carried out, and plasma concentrations of glucose, insulin, glucagon, and GLP-I were measured during the following 2 h. IVGTT together with GLP-I infusion significantly elevated insulin during 500 microgram/h SS but not during 1,000 microgram/h SS. Plasma glucagon was strongly depressed in all experiments. During 500 microgram/h SS, the glucose disappearance constant, Kg, was 0.49 +/- 0.03% per minute with GLP-I and 0.39 +/- 0.04% per minute with saline (n = 8, P = 0.004). With 1,000 microgram/h SS, Kg was 0.42 +/- 0.03% per minute with GLP-I and 0.40 +/- 0.03% per minute without (NS). In conclusion, when endogenous insulin secretion is held at a constant low level, which may be accomplished only with very large doses of SS, GLP-I has no effect on glucose elimination. Thus, an insulin-independent effect of GLP-I on glucose disposal could not be demonstrated.

Rotation of the anatomic regions used for insulin injections and day‐to‐day variability of plasma glucose in Type 1 diabetic subjects

AbstractThe paper by Bantle and colleagues from the University of Minnesota, Minneapolis, assesses the day‐to‐day variation in blood glucose concentrations following the commonly employed clinical practice or rotating anatomical sites for insulin injection.Twelve patients with insulin‐dependent diabetes had blood glucose profiles measured following insulin injections given in the abdomen for three days and then rotated around the arms, abdomen and thighs for three days using a cross‐over protocol. Considerable variation in terms of insulin absorption was found between the different injections sites and there was significantly less variability if insulin injections were confined to the abdomen alone.By following the common clinical practice of rotating sites for insulin injection, considerable day‐to‐day variation in blood glucose concentration can result from differences in insulin absorption. Therefore, the authors recommend that patients restrict insulin injections to a single site, preferably the abdomen, to reduce this variation and allow greater precision of insulin administration.The second paper by Jonathan Thow and Philip Home reviews the technique of insulin injection and, in particular, the depth of needle insertion. They observe that the change in the angle of insulin injection from 45° to a near perpendicular injection has important considerations in terms of insulin absorption, particularly for the thin patient.In such patients insulin may be injected almost into the muscle layer beneath the subcutaneous tissue, which will lead to variability in insulin absorption, often at a much quicker rate.A greater and more variable effect of physical exercise was also noted with intra muscular injection. Variability of insulin absorption after intra muscular injection also occurs between different types of insulin. Isophane insulins show considerable variability and are best not given via the intra muscular route.

Rotation of the anatomic regions used for insulin injections and day-to-day variability of plasma glucose in type I diabetic subjects

Rotation of the anatomic regions used for insulin injections and day-to-day variability of plasma glucose in type I diabetic subjects

Rotation of the Anatomic Regions Used for Insulin Injections and Day-to-Day Variability of Plasma Glucose in Type I Diabetic Subjects

Treatment of type I diabetes mellitus is hindered by the often large fluctuations in blood glucose concentration experienced by affected individuals. To determine to what extent day-to-day variation in blood glucose levels can be reduced if insulin is injected in the same anatomic region rather than in different regions using a rotational scheme, as is commonly recommended, 12 type I diabetic subjects were studied. Insulin injections were given in the abdomen for 3 days and rotated among arms, abdomen, and thighs for 3 days using a crossover design with random assignment of treatment order. Blood samples for measurement of plasma glucose levels were obtained at nine scheduled times on each day. Insulin dose, diet, and physical activity were held constant for each subject. During the abdominal injection period, the mean SD of plasma glucose levels and the mean variance of plasma glucose levels were both less at all nine time points than during the rotating injection period. Overall values for the SD of plasma glucose levels were 2.7 +/- 0.2 mmol/L for the abdominal injection period and 3.7 +/- 0.3 mmol/L for the rotating injection period. Overall values for the variance of plasma glucose levels were 9.2 +/- 1.4 mmol2/L2 for the abdominal injection period and 17.4 +/- 2.2 mmol2/L2 for the rotating injection period. We conclude that the common clinical practice of rotating the anatomic regions used for insulin injections increases day-to-day variation in blood glucose concentration. Use of a single anatomic region, eg, the abdomen, for all insulin injections may reduce this variation and allow greater precision in the adjustment of insulin doses.

Sorbitol accumulation is altered in type 1 (insulin-dependent) diabetes mellitus.

Intracellular sorbitol accumulation has been implicated as an aetiological factor for many of the complications of diabetes mellitus. Erythrocyte sorbitol is found in higher concentration in Type 1 (insulin-dependent) diabetic patients than in normal subjects. When sorbitol accumulation is corrected for its immediate precursor glucose (sorbitol/glucose ratio), the polyol accumulation remains significantly greater in erythrocytes from the Type 1 diabetic. Erythrocytes from Type 1 diabetic patients exposed to normal extracellular glucose concentrations for 3 h in vitro, accumulate more sorbitol and fructose than normal cells in the same incubation system. Near-normalization of plasma glucose in Type 1 diabetic patients for 12 h did not result in normal erythrocyte sorbitol levels. The increased sorbitol accumulation in erythrocytes from Type 1 diabetic subjects may reflect similar activity in the lens and nerve in long-standing diabetes. This increased sorbitol production was found in most, but not all, individuals with diabetes and appears to be an acquired characteristic. Those factors influencing enhanced tissue sorbitol accumulation may be important in the aetiology of diabetes-associated complications.