Fifty-two normal non-obese males and 77 male offspring of two diabetic parents, aged 15-72 years, were studied to identify possible reasons for discordance between the oral glucose tolerance test (OGTT) and hemoglobin A1c (Hb A1c). Subjects were classified into four study groups: group 1 (n = 83), normal OGTT and normal Hb A1c; group 2 (n = 19), normal OGTT and abnormal Hb A1c; group 3 (n = 9), abnormal OGTT and normal Hb A1c; and group 4 (n = 18), abnormal OGTT and abnormal Hb A1c. Glucose and insulin response were analyzed in each study group. Group 2 showed slightly higher mean glucose areas during the first 60 min of OGTT testing when compared with group 1 (P less than 0.01). Insulin levels, insulin areas and insulin/glucose regression coefficients on group 2 did not differ significantly from group 1 during OGTT. Group 3 showed significantly higher mean blood glucose levels than subjects in group 1 (P less than 0.0001) or group 2 (P less than 0.001), but significantly lower mean blood glucose levels than subjects in group 4 (P less than 0.04) throughout the OGTT. During the OGTT, group 3 showed marked absolute hyperinsulinism when compared with all other groups (P less than or equal to 0.002). Also, relative hyperinsulinism in group 3 was suggested by the elevated insulin/glucose regression coefficient (1.86 +/- 0.50) when compared with group 1 (1.17 +/- 0.09), group 2 (0.92 +/- 0.011) or group 4 (0.55 +/- 0.17) (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Turner's syndrome and carbohydrate metabolism. I. Impaired insulin secretion after tolbutamide and glucagon stimulation tests: evidence of insulin deficiency.

Tolbutamide (25 mg/kg: maximum 1 mg) intravenously (IV) and glucagon (0.03 mg/kg; maximum 1 mg) intramuscularly (IM) were given sequentially to 12 untreated girls with XO-Turner's syndrome (ages 6.5 to 17.0 years) and to ten female siblings (ages 8.0 to 16.7 years) to evaluate blood sugar (BS), plasma free fatty acids (FFA), serum immunoreactive insulin (IRI), and growth hormone (IRGH) responses to these insulinogenic secretagogues in order to appreciate any differences of genotypes on carbohydrate metabolism within identical family backgrounds. Seven of 12 patients with Turner's syndrome (58%) but none of the siblings were 20% or more overweight for height. There was a family history of diabetes mellitus in 7 to 12 patients (58%). The results showed significant elevations of mean FFA levels and decreased mean IRI responses to both insulinogenic stimuli without differences in mean BS or serum IRGH responses in the Turner's syndrome patients when compared to the controls. Three of 12 patients (25%) had abnormally elevated and prolonged blood sugar responses to IM glucagon. These findings show a significant incidence of abnormal carbohydrate and lipid metabolism and insulin deficiency in untreated patients with XO-Turner's syndrome when compared to normal female siblings and implicate this chromosomal defect in the impaired insulin secretion.

Adolescent↗

PubMedDate not supplied

Is insulin the link between hypertension and obesity?

Oral glucose tolerance tests with plasma glucose and insulin determinations were performed on 195 patients with impaired glucose tolerance. Patients were divided into three groups according to blood pressure levels: normal, below 140/90 mm Hg; diastolic hypertension, diastolic pressure above 90 mm Hg; and systolic hypertension, systolic pressure above 140 and diastolic pressure below 90 mm Hg. Sex, age, and glucose levels were similar among the groups. By contrast, serum insulin levels were significantly elevated for the patients with diastolic hypertension (p less than 0.01). This difference persisted after correction for body weight. These results suggest a causal relationship between the level of circulating insulin and diastolic blood pressure, and support the concept that hyperinsulinemia may be the common link in the clustering of hypertension, diabetes, and obesity.

Adult↗

PubMedDate not supplied

Hemoglobin A1c compared with three conventional measures of diabetes control.

Control of diabetes was studied during an 8-wk camp program in 18 insulin-dependent counselors with a mean age of 19.3 yr and a mean duration of diabetes of 11.4 yr. A composite score was obtained for each subject derived from three factors: percent sugar-free urine tests, 24-h glucose excretion as percent of carbohydrate intake, and mean preprandial blood glucose (MPBG). The mean hemoglobin A1c (HbA1c) at the end of the period was 8.3 +/- 1.6% (+/ SD) (normal range, 4-6%). Scores ranging from 24 (fair control) to 45 (excellent control) showed a significant inverse correlation with HbA1c (r = 0.807, P less than 0.001) and MPBG (r = -0.674, P less than 0.01). HbA1c showed a significant correlation with the MPBG (r = 0.693, P less than 0.01). The HbA1c level was predicted better by percent sugar-free urine tests than by the 24-h glucose excretion. Thus it appears that accurate quantification of control may be obtained by using a scoring system. Critical comparison of HbA1c levels to various glycemic indices may provide useful alternatives for estimating diabetes control.

Adolescent↗

PubMedDate not supplied

Use of a physiologic pharmacokinetic model of glucose homeostasis for assessment of performance requirements for improved insulin therapies.

Methods are presented for assessing insulin therapies using a physiologic pharmacokinetic model of glucose homeostasis in man. The model is composed of simultaneous differential equations that represent physiologic compartments and spaces in which glucose and insulin are distributed and undergo metabolic reactions. The model is used to simulate clinical experiments in which blood glucose concentration is controlled by artificial device therapies. Predictions of the theoretical model for responses of normal and diabetic individuals to standard intravenous and oral glucose tolerance tests are compared to clinical data. Reasonable agreement is obtained between predictions of the computer simulations and clinical data for normal individuals. The responses of a diabetic person to oral glucose tolerance tests are simulated by removal of the pancreas from the glucose homeostasis model and introduction of insulin into the model by a prescribed therapy. Model simulations reaffirm expectations concerning the poor blood glucose control attainable by intramuscular insulin injection. Simulations of blood glucose regulation by an artificial pancreas using closed-loop feedback control for controlling insulin delivery rate reveal hyperinsulinemia that results in a net shift in the deposition of a glucose load from liver to peripheral tissues. Simulations of this system in which the time delay for glucose measurement is varied from 1.5 to 30 min show that increases in sensor delay result in progressive loss in glucose regulation, exacerbation of hyperinsulinemia, and increased insulin requirements.

Blood Glucose↗

PubMedDate not supplied

Measurement of glucose concentration in the presence of coreactants with a platinum electrode.

An implantable glucose sensor is being developed that is based on the use of a high-area platinum electrode. The sensor is operated in a controlled potential mode, in which the potential of the platinum working electrode versus an unpolarized reference electrode is periodically varied according to a preselected voltage-time regimen. The change in potential is accompanied by a flow of current between the platinum working electrode and a counter-electrode. This current serves to periodically rejuvenate the electrode surface and to provide a signal that is proportional to the glucose concentration. A method for analyzing this signal has been developed, the compensated net charge (CNC) method, that involves integration of the current over one complete potential cycle. This method significantly improves both the sensitivity and selectivity for determining glucose in the presence of the normal physiologic coreactants. For a solution containing glucose, amino acids, and urea, a change in glucose concentration from 50 to 150 mg/dl gives about a 50% change in the net charge. A change in the urea concentration from 20 to 40 mg/dl has no effect on the net charge. A change in the amino acids concentration from 35 to 65 mg/dl has little effect on the net charge above a glucose concentration of about 100 mg/dl. Negligible effects on the net charge have also been found for creatinine (0-1.5 mg/dl) and uric acid (0-4 mg/dl).

Amino Acids↗

PubMedDate not supplied

Improvement of lipid status in diabetic boys: the 1971 and 1979 Joslin Camp lipid levels.

Since 1972, young type I diabetic patients seen by Joslin Clinic physicians have been advised to use a low cholesterol diet with a high proportion of polyunsaturated fat. Mean fasting cholesterol and triglyceride levels at admission to the Joslin Boys Camp for the years 1971 (N = 129) and 1979 (N = 79) were compared. In 1979, the mean cholesterol level was lower by 44 mg/dl (P less than 0.001) and the mean triglyceride by 21 mg/dl (P less than 0.001) compared with 1971. The incidence of hyperlipoproteinemia decreased from 21.6% to 7.6% with a complete disappearance of types IV and V during the same period. A decrease in the development of arteriosclerotic cardiovascular diseases in type I diabetic patients might be anticipated from this diet modification.

Adolescent↗

PubMedDate not supplied

Effect of acute blood loss on glycosylated hemoglobin determinations in normal subjects.

Nondiabetic adult subjects (N = 12) were studied to determine the effect of an approximately 450-ml acute blood loss upon glycosylated hemoglobin measurements. After blood loss, the hematocrit significantly decreased by week 1 (P less than 0.001) and the reticulocyte count peaked by week 2. All glycosylated hemoglobins measured showed significant decreases post blood loss. The nadir was at week 4 for total A1, A1c, and irreversible A1c by high-pressure liquid chromatography (HPLC), and at week 6 for irreversible A1 by HPLC and A1 by electrophoresis. The mean percent decrease in glycosylated hemoglobins ranged from 4.6% (irreversible A1 by HPLC) to 8.6% (total A1c by HPLC).

Adult↗

PubMedDate not supplied

Alterations in plasma lipids in the presence of mild glucose intolerance in the offspring of two type II diabetic parents.

Plasma lipids and oral glucose tolerance were determined in 67 normal control subjects (age range 19-67 yr) and 150 individuals (17-69 yr) who were offspring of two type II diabetic parents. Age- and weight-adjusted analyses of covariance were performed for lipids and for glucose and insulin responses. For both men and women, the mean concentrations of total, low-density-, and high-density-lipoprotein-cholesterol and of triglycerides in the offspring with normal glucose tolerance (N = 109) were similar to respective controls. For offspring with abnormal glucose tolerance (N = 41), the mean levels of total cholesterol, LDL-cholesterol, and triglycerides were significantly elevated (P = 0.02 or less) in women but not in men. The mean HDL-cholesterol levels were 20% lower and LDL/HDL-cholesterol ratios 60% greater in women with abnormal glucose tolerance, whereas no significant differences existed for any of the lipid fractions in men, compared with respective controls. Both men and women with abnormal glucose tolerance had a comparable magnitude of hyperglycemia as well as hyperinsulinemia. These observations indicate that significant alterations in plasma lipids exist in individuals with mild, asymptomatic glucose intolerance and there are important sex differences in lipid metabolism in the early stage of diabetes, despite comparable degrees of glucose intolerance and insulin responses.

Adolescent↗

PubMedDate not supplied

Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4.

In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.

Adolescent↗

PubMedDate not supplied

[Urinary excretion of insulin].

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Age Factors↗