Mean Plasma Glucose Levels Research Articles

Macular Blood Flow Response to Acute Reduction of Plasma Glucose in Diabetic Patients Measured by the Blue Light Entoptic Technique

The response of retinal blood flow to acute reduction in plasma glucose levels was studied in 20 poorly controlled type I diabetic patients. Perifoveal flow velocity was determined, using the blue-light entoptoscope, and arterial calibers measured, using a computer-aided digitizing system. Mean plasma glucose level was lowered from 17.7 ± 4 to 7.0 ± 1 mmol/l after a subcutaneous insulin infusion and measurements taken at both glucose levels. The autoregulatory change induced by breathing 60% oxygen at the two plasma glucose levels also was compared. Mean flow velocities were 0.54 ± 0.28 mm/ sec at a high plasma glucose level compared with 0.55 ± 0.32 mm/sec at a low plasma glucose level, whereas hyperoxia reduced these by 16.58 and 16.71%, respectively. No significant difference in the responses of arterial diameters to hyperoxia between the two glucose levels was found. The authors conclude that acute reduction in plasma glucose level in this group of patients is not associated with significant changes in macular blood flow or in alteration in autoregulation.

POST-LOAD PLASMA GLUCOSE AND CANCER MORTALITY IN MIDDLE-AGED MEN AND WOMEN

The relation of post-load plasma glucose to 12-year cancer mortality was studied in 11,521 white men and 8,591 white women aged 35-64 years at entry in the Chicago Heart Association Detection Project in Industry. There were 298 deaths in which cancer was the underlying cause in men and 186 such deaths in women. Plasma glucose levels at baseline measured one hour after a 50 g oral glucose load were positively related to cancer mortality in men but not in women. This increased mortality in men persisted after controlling for age, body mass index, smoking, serum cholesterol, systolic blood pressure, education, and anti-hypertensive treatment. A site-specific analysis of the male cancer deaths demonstrated higher mean plasma glucose levels for decedents for nearly all sites except oral cancers, liver cancer, and other respiratory cancers. For women, elevations existed for those who died of colon, lung, and hematologic/lymphatic tumors, but not for most other sites. The associations between baseline post-load plasma glucose levels and cancer mortality were similar for earlier and later cancer deaths, which indicates that incipient or occult neoplasm at baseline was not responsible for elevated glucose levels in men who subsequently died of cancer. Cancer mortality rates were also higher for those with a clinical diagnosis of diabetes than for those without, but the numbers of persons with diabetes were small as were the numbers of cancer deaths (19 in the men and 10 in the women).

Triphasic Randomized Clinical Trial: Comparison of effects on carbohydrate metabolism

One hundred thirty women were randomly assigned to treatment with one of three triphasic oral contraceptives and 43 women using nonhormonal methods served as controls for a 6-month study of the metabolic effects of these formulations. One of the oral contraceptives contained ethinyl estradiol and levonorgestrel, and the other two contained ethinyl estradiol and norethindrone. Compared with pretreatment assessment, all three triphasic oral contraceptives produced small increases in the mean plasma glucose levels that were statistically significant but clinically unimportant. No subjects had abnormal glucose response curves in glucose tolerance test results. Compared with pretreatment assessment, all of the oral contraceptive preparations produced small increases in the mean insulin levels at 3 months but not at 6 months. Overall there were no statistically significant differences among the three formulations in their effects on carbohydrate metabolism as measured by glucose or insulin levels after 6 months of treatment.

Insulin and C-Peptide Secretion in Non-Obese Patients with Polycystic Ovarian Disease

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

A preliminary trial of the programmable implantable medication system for insulin delivery.

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years.

Insulin secretion and sensitivity in hyperthyroidism.

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.

Prognostic Importance of Admission Plasma Glucose in Diabetic and Non-diabetic Patients with Acute Myocardial Infarction

We assessed the relationship of plasma glucose concentrations measured on admission to mortality during the acute phase of myocardial infarction in 143 diabetic patients and 277 patients without a previous history of diabetes. Mortality in hospital in patients not known to have diabetes increased significantly from 4 per cent in patients with admission plasma glucose below 8 mmol/l to 35 per cent in patients with admission plasma glucose above 11 mmol/l. In diabetic patients the mortality increased with increasing admission plasma glucose but the difference was not significant. In patients with diabetes mean admission plasma glucose levels of the survivors and those who died were similar, whilst in the non-diabetic group the mean plasma glucose levels of the patients who did not survive were significantly higher than those of the survivors. Stepwise logistic regression analyses identified admission plasma glucose level as an important predictor of mortality in the non-diabetic group but not in the diabetic patients. Plasma glucose level on admission is an important prognostic indicator in non-diabetic patients, in that hyperglycaemia is associated with a higher mortality. In diabetic patients a clear relationship between admission plasma glucose and mortality was not demonstrated.

Oxygen Free-Radical Scavengers and Immune Destruction of Murine Islets in Allograft Rejection and Multiple Low-Dose Streptozocin-Induced Insulitis

We examined the effects of desferrioxamine (DFX), a potent inhibitor of the formation of oxygen-derived hydroxyl radicals, and nicotinamide (NIC), a poly(ADP-ribose) synthetase inhibitor and a weak free-radical scavenger, on two models of immune destruction of murine islets [i.e., allograft rejection and multiple low-dose streptozocin (STZ)-induced insulitis]. Freshly isolated or low-temperature-cultured BALB/cJ islets were transplanted beneath the kidney capsules of C57BL/6J recipients. The recipients were treated with NIC alone (500 mg.kg-1.day-1), DFX alone (4.2 mg/day x 14 days), or NIC + DFX. Only recipients treated with NIC + DFX, receiving cultured islets, showed a mean graft survival time significantly longer than control mice receiving freshly isolated or cultured islets. Control CD-1 mice treated with multiple low doses of STZ developed insulitis and diabetes. Treatment with NIC alone, DFX alone, or NIC + DFX decreased the severity of hyperglycemia relative to the controls. Treatment with DFX alone was more effective than NIC alone or NIC + DFX. Only the group treated with DFX alone had a lower incidence of diabetes (mean plasma glucose level greater than 200 mg/dl) than the controls after 4 wk. Histologically, islets from control mice showed severe insulitis, islet destruction, and absence of stainable insulin, whereas islets from DFX-treated mice showed only mild peri-insulitis and a relative preservation of beta-cell granulation. Our study showed that NIC and DFX partially protect islets from immune destruction in allograft rejection and in low-dose STZ-induced insulitis. Apparently, hydroxyl radicals play important roles in both of these models.

The Effect of Asymptomatic Nocturnal Hypoglycemia on Glycemic Control in Diabetes Mellitus

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.

Peripheral insulin parallels changes in insulin secretion more closely than C-peptide after bolus intravenous glucose administration.

The changes in peripheral serum insulin and plasma C-peptide levels and in the insulin secretory rate in response to iv glucose (0.5 g/kg BW) administration were studied in seven normal subjects. Insulin secretory rates were calculated according to a two-compartment model of distribution for C-peptide, using individual C-peptide kinetics calculated from iv bolus injections of biosynthetic human C-peptide. The mean plasma glucose level increased from a fasting level of 5.1 +/- 0.1 (+/- SE) to a peak of 24.0 +/- 1.0 mmol/L at 3 min and reached basal levels 101 +/- 6 min after glucose administration. The mean serum insulin value increased from 50 +/- 12 to a peak of 405 +/- 58 pmol/L at 3 min and then declined to fasting levels 139 +/- 14 min after the stimulus. In contrast, the mean plasma C-peptide level increased from 390 +/- 50 to a peak of 1460 +/- 210 pmol/L at 3 min and only began declining 45 min after glucose administration, reaching fasting levels 191 +/- 15 min after the stimulus. The mean insulin secretory rate increased from 69.8 +/- 19.9 to a peak of 1412.7 +/- 159.1 pmol/min at 3 min (15.3 +/- 2.5-fold elevation over baseline) and reached basal levels 135 +/- 12 min after the stimulus. The clearance of endogenous insulin during the basal period (2.505 +/- 0.365 L/min) and that during the 4 h after the stimulus (2.319 +/- 0.230 L/min) were similar. In conclusion, after bolus iv glucose administration: 1) the insulin secretory rate is more closely represented by changes in peripheral serum insulin than in plasma C-peptide levels; and 2) no change in endogenous insulin clearance occurs.

Effect of helper and/or cytotoxic T-lymphocyte depletion on low-dose streptozocin-induced diabetes in C57BL/6J mice.

The low-dose streptozocin (STZ) model of diabetes has been reported to involve direct STZ beta-cytotoxicity and/or immunologically mediated beta-cell destruction. Because the T-lymphocyte dependency of such a model is controversial, we further assessed the role of T-lymphocytes by determining the occurrence and magnitude of hyperglycemia as well as the pancreatic insulin contents in both STZ-injected nude C57BL/6J male mice and STZ-injected euthymic C57BL/6J male mice selectively depleted in helper and/or cytotoxic T-lymphocytes with monoclonal antibodies (MoAbs). The effectiveness of MoAb treatment was assessed in lymph node cells by flow-microfluorometry analysis and in spleen cells by concanavalin A stimulation, allospecific cytotoxic T-lymphocyte activity, and T-lymphocyte lymphokine production. Sixteen days after the first STZ injection, hyperglycemia (plasma glucose greater than 200 mg/dl) occurred in significantly fewer helper T-lymphocyte-depleted mice (P less than .005) or helper and cytotoxic T-lymphocyte-depleted mice (P less than .001) than in non-MoAb-treated mice. However, a progressive increase in the number of mice with hyperglycemia ensued in all MoAb-treated groups, and 2 mo after STZ was administered, the prevalence of hyperglycemia, mean plasma glucose levels, and pancreatic insulin contents did not differ significantly from the values obtained in the non-MoAb-treated animals. Similarly, STZ-injected C57BL/6J male nude mice developed hyperglycemia that was associated with a marked decrease in pancreatic insulin contents on a time course comparable with that of STZ-injected euthymic C57BL/6J male mice depleted in helper or in helper and cytotoxic T-lymphocytes by MoAbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in CD-1 mice.

Multiple i.p. injections of low-dose streptozotocin (40 mg/kg) produce insulitis, beta cell destruction, and diabetes in male CD-1 mice. Recent data also suggest that macrophages figure in the low-dose streptozotocin model. Because other recent studies have shown that essential fatty acid deficiency prevents autoimmune nephritis in mice, decreases the number of resident Ia-positive glomerular macrophages, and decreases the elicitation of macrophages into the glomerulus in inflammation, we examined the effect of essential fatty acid deficiency on the incidence and severity of insulitis and diabetes in CD-1 mice treated with low-dose streptozotocin. Streptozotocin-treated mice on the control diet uniformly developed diabetes (19/19). Essential fatty acid-deficient mice treated with streptozotocin did not develop diabetes (1/13). Mean plasma glucose levels for the control and essential fatty acid-deficient mice were 384.5 +/- 23.6 and 129.1 +/- 15.5 mg/dl, respectively, at the end of 1 month. To discern whether essential fatty acid deficiency prevented the streptozotocin-induced beta cell injury or the inflammatory response to injured beta cells, mice were repleted with daily injections of 99% pure methyl linoleate beginning 3 days after the last streptozotocin injection. These mice also quickly developed severe (3/4) or mild (1/4) diabetes. Histologic examination of the pancreata of control mice or repleted mice showed marked insulitis and beta cell destruction; in contrast, the pancreata of essential fatty acid-deficient mice showed preservation of beta cells and only focal mild peri-insulitis. Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in low-dose streptozotocin-treated CD-1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.

Fructosamine in the management of gestational diabetes

The role of maternal serum fructosamine estimation in the management of gestational diabetes was assessed in 78 consecutive patients over a 3-year period. Fructosamine results correlated significantly with mean plasma glucose levels over a 1- to 3-week interval, with the closest association being in the preceding week. Eighty-five percent of women with gestational diabetes had peak serum fructosamine levels above the normal range. If maternal levels exceeded 3.2 mmol/L, there was an 88% chance of abnormal glucose tolerance post partum. Our aim of management was a serum fructosamine level <2.5 mmol/L; patients who achieved this goal by 35 to 37 weeks' gestation had fewer obese babies with lower cord insulin and C-peptide levels as compared with neonates of mothers with elevated fructosamine concentrations.

Effects of short-term insulin therapy upon therapeutic response to glipizide

The effect of glipizide alone and glipizide preceded by a short course of insulin therapy (10 weeks) was studied in 69 patients with non-insulin-dependent diabetes mellitus (NIDDM) in a 10-month study. The patients were obese, had poor glycemic control, and, in all patients, first-generation sulfonylurea therapy had failed. The majority were Mexican-Americans, an ethnic population with a high incidence of NIDDM and insulin resistance. Plasma glucose levels were monitored using the eight-point [Saarstedt] series. In the group receiving glipizide alone, mean fasting plasma glucose levels decreased from 255.9 mg/dl at baseline to 228.7 mg/dl at the end of the study; two-hour postprandial glucose levels decreased from 280.1 to 260.5 mg/dl; glycosylated hemoglobin decreased from 9.1 to 7.4 percent; and post-Sustacal C-peptide levels increased from 0.7 to 1.0 pmol/ml. In the group receiving insulin/glipizide, mean fasting plasma glucose levels decreased from 241.1 mg/dl at baseline to 217.0 mg/dl; two-hour postprandial glucose levels increased from 267.2 to 279.0 mg/dl; glycosylated hemoglobin decreased from 9.1 to 7.5 percent; and post-Sustacal C-peptide levels increased from 0.6 to 1.0 pmol/ml. At the end of 10 weeks, insulin administration was associated with a more rapid decrease in the levels of fasting plasma glucose, two-hour postprandial glucose, and glycosylated hemoglobin, but there was no significant difference between the two therapies by the end of the study. Both regimens had a positive influence on reducing the total cholesterol/high-density lipoprotein ratio. More patients in the group receiving insulin/glipizide withdrew from the study, which may have been due to difficulties associated with insulin administration. In conclusion, there does not appear to be a prolonged effect of insulin treatment on the post-receptor defect. Some patients in whom first-generation oral agents fail may not have to be given permanent insulin therapy, especially those with fasting plasma glucose levels of less than 200 mg/dl. There was no overall difference between these treatments with respect to glycemic control or lipoprotein profiles. In the interests of simplifying both therapy and monitoring, enhancing patient compliance, and achieving cost reductions, therapy with glipizide alone ultimately may be sufficient for cases in which immediate control is unnecessary (for example, patients with asymptomatic hyperglycemia, and in the absence of hyperlipidemia and vascular disease).

Evidence for Insulin Resistance in Nonobese Patients with Polycystic Ovarian Disease

In this study seven normal weight Indian patients with polycystic ovarian disease (PCOD) with no evidence of acanthosis nigricans and 7 age- and weight-matched normal Indian women were studied to determine whether PCOD patients were insulin-resistant. While all 14 women had normal glucose tolerance, the PCOD women had significantly higher mean plasma glucose levels at 30 and 60 min and higher mean incremental glucose areas [incremental areas: PCOD, 9.0 +/- 2.2 (+/- SEM); normal women, 4.0 +/- 0.8 mmol/L; P less than 0.05]. Insulin responses were significantly higher in the PCOD compared to normal women (incremental areas: PCOD, 623.8 +/- 78.3; normal women, 226.2 +/- 30.3 microU/mL; P less than 0.001). Both serum testosterone and androstenedione levels correlated with the insulin areas (r = 0.82; P less than 0.001 and r = 0.86; P less than 0.001, respectively). [125I] Insulin binding to erythrocytes revealed decreased maximum specific binding in the PCOD women (6.9 +/- 0.6%) compared to that in normal women (9.2 +/- 0.7%; P less than 0.02). While Scatchard analysis revealed similar receptor numbers, ID50 values demonstrated decreased receptor affinity in the women with PCOD. In conclusion, in the absence of acanthosis nigricans, nonobese patients with PCOD are insulin resistant, and this insulin resistance correlates with the hyperandrogenism.

The effects of one month high fructose intake on plasma glucose and lipid levels in non-insulin-dependent diabetes.

The effects of a high fructose diet on the control of blood glucose and serum lipids were studied in 10 non-insulin-dependent diabetic patients (mean age 64.4 years, mean duration of diabetes 5.6 years). Comparison was made following 28 days on the usual diabetic diet and 28 days during which 25% of the usual carbohydrate was substituted with fructose. There was no change in mean (+/- SEM) fasting plasma glucose (on usual diet 9.2 +/- 0.5 mmol/l, on fructose diet, 9.1 +/- 0.4 mmol/l), but there was a fall in mean plasma glucose levels at 30, 60, and 120 min in a 75 g OGTT following the fructose diet. There was no significant change in fasting lipids: on usual diet mean serum cholesterol 5.8 +/- 0.2 mmol/l, on fructose diet 5.6 +/- 0.2 mmol/l; serum triglyceride, on usual diet 1.3 +/- 0.1 mmol/l, on fructose diet 1.3 +/- 0.1 mmol/l; HDL cholesterol on usual diet 1.4 +/- 0.1 mmol/l, on fructose diet 1.4 +/- 0.1 mmol/l. Mean body weight did not vary significantly between the two diets. Incorporation of fructose into the diabetic diet may lower post-prandial glucose levels without disturbing serum lipids.

Metabolic Effects of Dietary Fructose and Sucrose in Types I and II Diabetic Subjects

To learn more about the metabolic effects of dietary fructose and sucrose, 12 type I and 12 type II diabetic subjects were fed three isocaloric (or isoenergic) diets for eight days each according to a randomized, crossover design. The three diets provided, respectively, 21% of the energy as fructose, 23% of the energy as sucrose, and almost all carbohydrate energy as starch. The fructose diet resulted in significantly lower one- and two-hour postprandial plasma glucose levels, overall mean plasma glucose levels, and urinary glucose excretion in both type I and type II subjects than did the starch diet. There were no significant differences between the sucrose and starch diets in any of the measures of glycemic control in either subject group. The fructose and sucrose diets did not significantly increase serum triglyceride values when compared with the starch diet, but both increased postprandial serum lactate levels. We conclude that short-term replacement of other carbohydrate sources in the diabetic diet with fructose will improve glycemic control, whereas replacement with sucrose will not aggravate glycemic control.

Regional cerebral glucose utilization during insulin-induced hypoglycemia in unanesthetized rats.

Regional cerebral glucose utilization (rCMRgl) was studied during insulin-induced hypoglycemia in unanesthetized rats. Rats were surgically prepared using halothane and nitrous oxide anesthesia and allowed 5 h to recover from the anesthesia before rCMRgl was measured. The rCMRgl was measured using [6-14C]glucose in a normoglycemic control group and two hypoglycemic groups, A (30 min after insulin injection) and B (2 h after insulin injection). The mean plasma glucose level was 7.03 mumol/ml in the normoglycemic group, 1.96 mumol/ml in hypoglycemic group A, and 1.40 mumol/ml in hypoglycemic group B. The rCMRgl in hypoglycemic group A decreased 8-18% in 17 brain regions measured; five changes were statistically significant. The rCMRgl in hypoglycemic group B decreased significantly in all but one of the brain regions measured; the decrease ranged from 15% in the pyramidal tract to 36% in the motor and auditory cortices. The rCMRgl in every brain region decreased when the plasma glucose level fell below 1.5-2.5 mumol/ml. No brain region could maintain rCMRgl at plasma glucose concentrations lower than predicted by regional glucose influx described in previous studies. Glucose utilization in all brain regions appears to be limited by the influx of glucose.

Basal Glucagon Replacement in Chronic Glucagon Deficiency Increases Insulin Resistance

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Preprogrammed intravenous insulin infusion in diabetic humans: metabolic consequences of altering meal size.

New implantable, variable-rate, intravenous insulin infusion systems offer the possibility of increased dietary flexibility in the treatment of diabetes mellitus. However, the development of insulin infusion algorithms required to maintain near-normal glycemia in the presence of a nonconstant diet first requires information concerning the metabolic response to meals of varying size when the insulin dose is fixed. With this goal in mind, we studied five type I diabetics aged 16-40 yr who were treated for 3 wk with a portable intravenous insulin infusion system. Initially, the patient's usual prescribed diabetic diet was provided, and an individual waveform of insulin infusion resulting in diurnal normoglycemia was defined for each meal. Subsequently, small (12% of total daily calories) and large (36% of total daily calories) versions of the regular breakfast (24% of total daily calories) were provided without change in the insulin infusion waveforms, and the resulting metabolic profiles were studied. The overall mean fasting plasma glucose levels before the meals of varying size were not significantly different, but the incremental rises in plasma glucose with the small (31 +/- 5 mg/dl), regular (48 +/- 7 mg/dl), and large (64 +/- 5 mg/dl) breakfasts varied directly with the meal size. The subsequent mean plasma glucose levels before the regular lunch were significantly different (P less than .05) after the small (50 +/- 4 mg/dl) and large breakfasts (131 +/- 9 mg/dl), compared with the regular breakfast (81 +/- 7 mg/dl). Despite these differences, the plasma glucose levels before dinner were virtually identical. We conclude that large variations in meal size produce glycemic changes in keeping with the caloric content of the meal.(ABSTRACT TRUNCATED AT 250 WORDS)