Normal Fasting Plasma Glucose Levels Research Articles

Splanchnic tissues play a crucial role in uremic glucose intolerance

Objective: Determine the mechanism of glucose intolerance in chronically uremic subjects. Design: Comparison of doubly labeled oral glucose tolerance tests. Subjects: Seven nondialyzed chronically uremic subjects (creatinine, 420 ± 104 μmol/L) and 7 healthy subjects, matched for age and body mass index. Intervention: Plasma glucose was labeled by an infusion of dideuterated glucose started 120 minutes before ingestion of 1 g/kg of naturally 13C-enriched corn starch glucose. Glucose levels and oxidation were monitored for 330 minutes after glucose ingestion. Results: Uremic subjects had normal fasting plasma glucose levels and impaired glucose tolerance with high plasma insulin ( P < .001 versus controls). Glucose tolerance was impaired because of an increased total rate of appearance of glucose (cumulated on 330 minutes: uremic, 1,231 ± 42 mg/kg/330 min, controls, 1,031 ± 64; P < .05). Peripheral glucose uptake was increased ( P < .05) because of an increased nonoxidative disposal ( P = .051). Conclusions: Although peripheral glucose uptake resisted the stimulatory effect of the high insulin levels, glucose tolerance was impaired through splanchnic metabolic disturbances: reduced splanchnic glucose uptake and increased endogenous glucose production. The respective contribution of these abnormalities remains to be determined.

Effects of changes in obesity and exercise on the development of diabetes and return to normal fasting plasma glucose levels at one-year follow-up in middle-aged subjects with impaired fasting glucose

Borderline diabetes, a precursory condition of diabetes, is an important issue in the prevention of diabetes. The aim of the present study was to clarify the effects of one-year changes in obesity and exercise on the development of diabetes or return to normal fasting plasma glucose (FPG) levels among middle-aged people with impaired fasting glucose (IFG) at baseline. Among those who attended a basic health examination in 1997, we selected 1,620 subjects who showed impaired fasting glucose (FPG of 110 mg/dl or higher) and had complete data on height, weight and exercise. At the one-year follow-up (in 1998), 1,099 of those subjects attended a health examination; FPG, height, weight and exercise were evaluated for 731 subjects. Subjects were classified into the following three groups, on the basis of changes in FPG during the year between the two examinations: developing diabetes (DM), remaining IFG, and returning to normal (WNL). Among those who were initially obese, there was a significant difference in the proportions of DM, IFG and WNL between those with and without improvement in obesity in the year preceding the follow-up (p<0.05). Those with improvement in obesity showed a significantly higher tendency to return to WNL than those without improvement in obesity. Multiple logistic regression analysis showed that those with improvement in obesity had a significantly higher odds ratio (2.17) to return to WNL (p=0.015). Among those who were initially not obese, there was no significant association between changes in obesity and developing DM or returning to WNL. No significant association was observed between changes in exercise and developing DM or returning to WNL. The present findings suggest that, among obese IFG subjects, improvement in obesity is associated with returning to normal plasma glucose. Weight control may be important for the normalization of borderline diabetes.

Cholesteryl ester transfer and cholesterol esterification in type 1 diabetes: relationships with plasma glucose

The activities of two crucial enzymes of reverse cholesterol transport, cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT), and their relationships with lipid profile and fasting plasma glucose were examined in 35 type 1 diabetic children. The CETP and LCAT activities were significantly lower (p<0.05) in the 4 subjects with normal fasting plasma glucose levels (<6.39 mmol/l) than in the 28 with high plasma glucose levels (CEPT activity, 10.63+/-3.81 vs. 32.18+/-13.94 nmol/ml h; LCAT activity, 25.52+/-4.53 vs. 39.52+/-12.52 nmol/ml h; both p<0.05). The subjects with high plasma glucose levels also had higher total and LDL-cholesterol than those with normal glucose levels. CETP activity was positively correlated with fasting plasma glucose, CETP concentration, LCAT activity, total cholesterol, free cholesterol, LDL-C, and LDL-cholesteryl ester, while negatively correlated with cholesteryl ester to free cholesterol ratio, LDL triglyceride to protein ratio, and LDL triglyceride to cholesteryl ester ratio. LCAT activity was found to positively correlate with CETP activity, total cholesterol, free cholesterol, LDL-C, CETP concentration, and LDL-cholesteryl ester, while it negatively correlated with cholesteryl ester to free cholesterol ratio. The results observed in type 1 diabetic subjects suggest that (1) accelerated LCAT and CETP activities may result in the accumulation of LDL-cholesteryl ester; and (2) fasting plasma glucose may be a major determinant of CETP activity.

Glucose peaks – the hidden danger in type 2 diabetes

Glucose peaks – the hidden danger in type 2 diabetes

Evaluation of WHO and NDDG criteria for impaired glucose tolerance

A 4-year prospective study on the natural history of IGT in South African Indians has allowed for the evaluation of the WHO and NDDG criteria for IGT, using the five groups for non-diabetic glucose tolerance recently recommended and relating these to the risk of diabetes development. Using WHO criteria, 128 subjects were classed IGT in a base-line survey (Year 0). The five recommended categories were applied to the OGTTs done between Year 1 and Year 4 of the study, when mid-test plasma (MPG) samples were also obtained. These categories included N-N (Normal by WHO and NDDG); N-ND1 (Normal by WHO, non-diagnostic level 1 by NDDG); N-ND2 (Normal by WHO, non-diagnostic level 2 by NDDG); I-ND3 (IGT by WHO, non-diagnostic level 3 by NDDG) and I-I (IGT by WHO and NDDG). The risk of diabetes development and the significance of the non-diagnostic category were evaluated by comparing the glucose tolerance status at Year 4 with the status at Year 1. In the cross-sectional evaluation at Year 1, of the 87 non-diabetic OGTTs analysed, 31% ( n = 27) were classified I-I, 34.5% ( n = 30) were classed N-N and 34.5% ( n = 30) were classified non-diagnostic [I-ND3 (23.1%); N-ND2 (8%); N-ND1 (3.4%)]. In the prospective analysis, of the 72 subjects who completed the study, 16 subjects developed NIDDM by Year 4; of these 13 subjects were classed I-I and 3 subjects I-ND3 at Year 1. The rate of diabetes development was highest in the I-I group (61.9%) and was significantly higher when compared with the I-ND3 group ( P < 0.01), N-N group ( P < 0.0001) and N-ND2 + N-ND1 group ( P < 0.01). The risk of diabetes development in the I-ND3 group (15.8%) did not differ significantly from that in the N-N group. The results of this study would suggest that the I-I group, which shows a significant risk of diabetes development, probably represents IGT. It would appear that the non-diagnostic categories (I-ND3, N-ND2 and N-ND1) which possess a lower risk of diabetes development than the I-I group, possibly represent groups whose glucose tolerance behaves more like Normal than IGT. Moreover, the results would support the view that the cut off point for normal fasting plasma glucose (FPG) levels of NDDG might be raised to < 7.8 mM. This study confirms the proposal that further studies relating to the natural history of IGT should include MPG samples in order to evaluate the true status of the NDDG non-diagnostic category.

Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1

Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (approximately 5-fold), hexose monophosphates (approximately 7- to 13-fold), inosine monophosphate (IMP) (approximately 15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; approximately 6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 +/- 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (approximately 95 mg/dl; 40 and 400 mU.m-2.min-1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK-2 and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates.

Autoantibodies in Black Women with Class A1or Class GB Diabetes Mellitus

No marker except repeated fasting glucose determinations has proven useful to ascertain prospectively which women with gestational diabetes mellitus will remain euglycemic by diet modification or will require insulin therapy. We screened 183 black women with gestational diabetes mellitus to determine if the presence of islet cell, mitochondrial, nuclear, DNA, parietal cell, smooth muscle, thyroid microsomal, thyroid thyroglobulin autoantibodies, or rheumatoid factor predicted the need for insulin therapy to maintain euglycemia in women with gestational diabetes mellitus. One hundred forty-two women maintained normal fasting plasma glucose levels with dietary modifications and 41 required institution of split-dose insulin therapy. We found no significant differences in the prevalence of these autoantibodies in black women with Class GB versus Class A1 diabetes mellitus. We conclude that screening for autoantibodies in women with gestational diabetes mellitus is not useful in determining which patients will subsequently require insulin therapy during their pregnancies.

Diabetic Chinese hamsters: metabolic effects of long term guar gum consumption

The effect of 13 weeks of guar gum or cellulose diet consumption upon metabolic parameters was examined in diabetic and control adult Chinese hamsters. Diabetic hamsters displayed typical diabetic metabolic profiles. Both 8% guar gum and 8% cellulose diets maintained body weights in all 4 groups during the study. Diabetic and control hamsters fed guar gum drank less water as the study progressed. At weeks 9 and 13, diabetic hamsters fed guar gum excreted less urine compared to those fed cellulose. Diabetic hamsters fed guar gum had reduced urinary glucose excretion at weeks 1, 9 and 13 compared to those fed cellulose. Control hamsters fed either diet had normal urine volumes with only traces of glucose. Similar fasting plasma glucose levels were measured initially for all diabetic hamsters; all 3 subsequent measurements revealed lower levels for the group fed guar gum. Control hamsters had normal fasting plasma glucose levels. Comparable fasting plasma insulin levels were measured for all diabetic hamsters; these levels increased during the study. Control hamster fasting plasma insulin levels were 3 times higher and did not change. Throughout the study, diabetic hamsters fed guar gum consistently had healthier metabolic profiles than those fed cellulose.

Injectable microencapsulated islet cells as a bioartificial pancreas

Rat islets encapsulated in semipermeable membranes remained viable in culture for 4 months. Multiple allotransplants of islets encapsulated in alginate-polylysine-polyethyleneimine membranes restored normoglycemia in recipient diabetic rats for most of a 90-day experimental period. Each individual transplant restored normal fasting plasma glucose levels for 15-20 d. The failure of the encapsulated islets was caused by an inflammatory response induced by polyethyleneimine. In contrast a single transplant of islets encapsulated in a biocompatible alginate-polylysine-alginate membrane restored normoglycemia in recipient animals for up to 10 months. Capsules with intact membranes and containing viable islets were recovered from the abdominal cavity 5 months post-transplantation. SEM studies on capsule membranes revealed essentially smooth surfaces. Differences between wet and dry wall thicknesses indicated that the membrane is a hydrogel, 4.00 +/- 0.28 micron thick in an aqueous environment. The clinical potential of transplanting cells encapsulated in biocompatible semipermeable hydrogel membranes is demonstrated by this study.

Diet-Induced Improvement of Abnormalities in Insulin and Glucagon Secretion and in Insulin Receptor Binding in Diabetes Mellitus*

Abstract The effect of weight loss and caloric restriction on plasma glucose concentration, insulin and glucagon secretion in response to oral and iv glucose and arginine infusions, and insulin binding to mononuclear cell receptors was examined in 10 subjects with newly diagnosed maturity-onset diabetes mellitus [DM; fasting plasma glucose, 260 ± 8 mg/dl (mean ± SE)] and in 10 nondiabetic control subjects. Initially, the insulin response to glucose was absent in the DM subjects, but a distinct response occurred after iv arginine (P < 0.001). Caloric restriction and weight loss led to restoration of normal fasting plasma glucose levels in the DM patients (98 ± 4 mg/dl; P < 0.001) and little change in the control subjects. Serum insulin levels in response to glucose in DM increased significantly after weight loss compared to initial values (P < 0.01) but showed no change in response to arginine. In contrast, in the control subjects, the serum insulin responses to glucose decreased significantly (P < 0.05). ...

Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: Responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels

Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal-caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied. Administration of glucose i.v. caused rapid suppression of total plasma IRG in normoglycemic and non-insulin-dependent hyperglycemic cirrhotic subjects. After administration of oral glucose, total plasma IRG was suppressed rapidly in normoglycemic cirrhotic subjects, while non-insulin-dependent hyperglycemic cirrhotic subjects exhibited delayed but prolonged suppression. Chromatography of selected plasmas with glucose-suppressed total IRG showed a major decrease in the 3500-mol wt component in every case. Exaggerated increments of plasma gastric inhibitory polypeptide were demonstrable in both groups of cirrhotic individuals after administration of oral glucose, and it is speculated that this peptide may contribute to stimulation of glucagon secretion in liver disease associated with insulin deficiency.

Relationship between the plasma glucose level and glucose uptake in the conscious dog

In the absence of a change in the pancreatic hormonal milieu, elevations in the normal fasting plasma glucose level have little effect on glucose clearance. In view of these data, and the previously established responsiveness of M to hormones, glucose clearance can be considered to represent a useful index of hormone action on glucose uptake in vivo. Care should be taken, however, when interpreting clearance data obtained under hypoglycemic conditions, since there is a possibility that clearance may spontaneously increase at very low plasma glucose levels.

The spontaneously diabetic Wistar rat (the ?BB? rat)

A longitudinal study of 51 weanlings from 5 litters of “BB” Wistar rats was undertaken to characterize the time course of the spontaneous diabetic syndrome. Nine rats developed overt diabetes. An abnormal glucose tolerance preceded the onset of the syndrome in 6 of these 9 rats. No other “clinical” or metabolic variable measured was predictive of the development of this syndrome. In these rats, the onset was remarkably abrupt, followed by rapid clinical deterioration with marked hyperglycaemia, glycosuria, ketonaemia and hypoinsulinaemia attained within 2 to 8 days. Pronounced insulitis was present in the early stages of the syndrome, resulting in complete B-cell destruction at the time of sacrifice at 7 to 40 days. Among the 42 littermates, 9 revealed sequential abnormalities in oral glucose tolerance tests performed at weekly intervals (to age 90–120 d) though remaining aglycosuric and maintaining normal fasting plasma glucose levels. In 7 of these rats, a milder form of the same islet inflammatory lesion seen in the overtly diabetic animals was present. Thus the new features identified are: 1) a time course of evolution from normoglycaemia to overt diabetes telescoped into a period of days, and 2) a “chemical” stage or form with an insulitis similar to that found in the early stages of overt diabetes.

Beta Cell Function During Insulin or Chlorpropamide Treatment of Maturity-onset Diabetes Mellitus

Maturity-onset diabetic patients usually have raised overnight-fasting plasma glucose levels associated with "normal" basal plasma insulin levels. The basal hyperglycemia is proportional to the degree of insulin deficiency. Basal insulin or C-peptide levels become subnormal if normal fasting plasma glucose levels are attained with insulin. Basal hyperglycemia is probably a compensatory response to maintain near-normal basal insulin levels. A logical therapy of maturity-onset diabetes is to produce basal normoglycemia by means of a constant basal insulin supplement, which can be provided by ultralente insulin. The reduced insulin response of diabetics to intravenous glucose is slightly increased when basal normoglycemia is established, suggesting that the high plasma glucose levels compromise beta cell function. The insulin response to meals in a mild diabetic is not affected by mild hyperglycemia but can be depleted if gross hyperglycemia occurs. Maintenance of normoglycemia then allows beta cell "recovery". In mild diabetics (c. less than 9 mmol per liter basal plasma glucose), chlorpropamide sufficiently stimulates beta cell secretion so that basal normoglycemia can be produced. The C-peptide response to meals is improved, whereas comparable reduction of the plasma glucose with insulin does not alter the meal response. Thus basal normoglycemia can be produced by "resting" beta cells with a basal insulin supplement or by stimulating them with sulfonylurea therapy.

INCREASED FREQUENCY OF DIABETES MELLITUS IN PATIENTS WITH HUNTINGTON'S CHOREA

Six of ten patients with documented Huntington's chorea had an unusual form of diabetes mellitus characterised by marked hyperglycæmia, resistance to ketosis, absence of glycosuria, and markedly elevated insulin levels in response to the administration of glucose or arginine. Four patients (group I) had normal fasting plasma glucose and insulin levels and a normal response to the glucose-tolerance test (G.T.T.). The other six (group II) had normal fasting glucose levels but slightly elevated fasting insulin levels; the G.T.T. was abnormal. In group I arginine resulted in normal glucose and insulin rise, and peak insulin at 30 minutes was 44·0±6·1 μU. per ml. In group II, despite a similar degree of glucose elevation after arginine, peak insulin at 30 minutes was 96·3±21·3 μU. per ml. Clinically no correlation other than duration of disease could be made with the metabolic findings. Whether these data may be explained by an abnormal genetic linkage between Huntington's chorea and carbohydrate intolerance, or by a primary imbalance of biogenic amines, is not yet established.