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Query: UMLS:C0011849 (diabetes)
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Continuous subcutaneous insulin infusion (CSII) with a portable pump was compared to unchanged conventional treatment (UCT) in long-term treated patients with IDDM in order to evaluate changes in glucose homeostasis, metabolites, hormones and quality of life. We found that the mean blood glucose values, measured at home, and the HbA1c values were significantly lower in the CSII group compared to the UCT group. The improved control during CSII was followed by a nearly normalization of the diurnal pattern of FFA and ketone bodies in plasma. Plasma free insulin values were significantly higher in the morning (fasting) during CSII compared to UCT, whereas the mean diurnal concentrations and the diurnal pattern were identical in the 2 groups. Both peak values of growth hormone during the day and the fasting values were significantly lower in the CSII group compared to the UCT group. In patients treated with the insulin pump (CSII) the wellbeing (quality of life) was estimated to be significantly improved. Two patients developed ketoacidosis during CSII, whereas 2 controls (UCT) were hospitalized with hypoglycemic coma. We conclude that insulin pump treatment for 6 months results in a near normalization of glucose and FFA metabolism, resulting in an improved quality of life. The improved control seems not to be explained by a change of the diurnal pattern of plasma insulin. However, the higher morning values may be of significant importance.
Diabetes Res 1985 Jan
PMID:Insulin pump treatment: effect on glucose homeostasis, metabolites, hormones, insulin antibodies and quality of life. 388 95

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.
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PMID:Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans. 389 86

Plasma glucose, insulin, and FFA concentrations were determined in 15 normal subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM) from 0800 to 1600 h. Breakfast and lunch were consumed at 0800 and 1200 h, respectively, and plasma concentrations were measured at hourly intervals from 0800-1600 h. Plasma glucose concentrations between 0800 and 1600 h were significantly elevated in patients with NIDDM, and the higher the fasting glucose level, the greater the postprandial hyperglycemia. Hyperglycemia in patients with NIDDM was associated with plasma insulin levels that were significantly higher (P less than 0.001) than those in normal subjects, and substantial hyperinsulinemia occurred between 0800 and 1600 h in patients with mild NIDDM (fasting plasma glucose concentrations, less than 140 mg/dl). Both fasting and postprandial FFA levels were also increased in patients with NIDDM (P less than 0.001), and the greater the plasma glucose response, the higher the FFA response (r = 0.70; P less than 0.001). However, there was no significant correlation between plasma insulin and FFA concentrations. More specifically, hyperinsulinemic patients with mild diabetes (fasting plasma glucose, less than 140 mg/dl) maintained normal ambient FFA levels, while FFA concentrations were significantly elevated in patients with severe NIDDM (fasting plasma glucose, greater than 250 mg/dl), with insulin concentrations comparable to those in normal subjects. These results demonstrate that patients with NIDDM are not capable of maintaining normal plasma FFA concentrations. This defect in FFA metabolism is proportionate to the magnitude of hyperglycemia and occurs despite the presence of elevated levels of plasma insulin. These results are consistent with the view that insulin resistance in NIDDM also involves the ability of insulin to regulate FFA metabolism.
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PMID:Ambient plasma free fatty acid concentrations in noninsulin-dependent diabetes mellitus: evidence for insulin resistance. 390 Jan 20

The hormonal responses to low-level exercise in pregnancy have been studied in 13 insulin-requiring diabetic patients and 42 control subjects. We found no significant changes in plasma glucose, epinephrine, glucagon, or FFA with this level of exercise in the study group and control subjects; but plasma norepinephrine showed a significant increase with exercise. This type of exercise appears to be safe and could serve as a model for exercise prescription for attaining improved glucose tolerance in pregnant diabetic women.
Diabetes 1985 Jun
PMID:Hormonal responses to exercise in diabetic and nondiabetic pregnant patients. 399 70

The ability of exercise and diet to modify the effects of moderate streptozotocin-induced insulin deficiency on triglyceride metabolism has been studied in the rat. Insulin-deficient rats allowed to run spontaneously in exercise wheel cages had significantly lower (P less than 0.001) plasma glucose levels (187 +/- 19 mg/dl) than either sedentary (374 +/- 24 mg/dl) or sucrose-fed (450 +/- 13 mg/dl) diabetic rats, despite the fact that plasma insulin levels were comparable in all these groups. Plasma triglyceride (TG) levels in exercise-trained rats with diabetes (51 +/- 5 mg/dl) were actually lower than in control rats with normal glucose tolerance (90 +/- 14 mg/dl). In contrast, plasma TG levels were higher than control levels in diabetic sedentary rats (128 +/- 11 mg/dl), and severe hypertriglyceridemia developed in sucrose-fed diabetic rats (369 +/- 35 mg/dl). The ability of exercise training to attenuate diabetic hypertriglyceridemia, which was observed in both chow-fed and sucrose-fed rats, was secondary to a decrease in TG secretion, and appeared to be related to lower plasma FFA concentrations. In contrast, the accentuation of diabetic hypertriglyceridemia seen in sucrose-fed rats was related to a defect in TG catabolism. Adipose tissue lipoprotein lipase (LPL) activities were essentially identical in all diabetic rats, suggesting that the observed difference in TG kinetics could not be attributed to concomitant increases or decreases in adipose tissue LPL activity. These results emphasize the powerful impact of exercise and diet on TG metabolism in rats with moderate degrees of insulin deficiency.
Diabetes 1983 Jan
PMID:Effect of exercise and diet on triglyceride metabolism in rats with moderate insulin deficiency. 633 2

The metabolic response to exercise in insulin-dependent diabetic (IDD) man was assessed during continuous insulin infusion using the subcutaneous (CSII), intravenous (CIVII), and intraperitoneal (CIPII) routes. During the basal period, plasma glucose levels were higher with CIPII (153 +/- 17 mg/dl) than with CSII (117 +/- 13 mg/dl) or CIVII (118 +/- 17 mg/dl). Basal free insulin concentrations were similar for CSII (12.3 +/- 10 microU/ml) and CIVII (12.4 +/- 1.4 MicroU/ml) but lower in CIPII (8.5 +/- 1.0 microU/ml, P less than 0.05). Exercise on a stationary bicycle at 75 W for 60 min produced a decline of plasma glucose in each protocol that was significantly only during CIVII (55 +/- 11 mg/dl, P less than 0.01). Insulin levels remained unchanged throughout the study period in all protocols. In normals, insulin values decreased during exercise and remained below basal levels through the recovery period (P less than 0.05), while plasma glucose remained unchanged. Plasma glucagon and epinephrine levels were similar in all protocols and remained unchanged with exercise, while plasma norepinephrine tended to be higher than normal in all diabetic subjects. Significant differences between normal and diabetic subjects (P less than 0.05) were observed for blood ketone bodies, while blood lactate, glycerol, and plasma FFA were similar. Normalization of intermediary metabolites occurred only with CIVII. Continuous insulin infusion provides near-normal glycemic and metabolic control before, during and following exercise in IDD man. However, to produce normal blood concentrations of intermediary metabolites during exercise, the insulin infusion rate may be excessive in terms of its hypoglycemic effect. CSII appears to be a safe, accessible, and adequate method for treating diabetic man during exercise.
Diabetes Care
PMID:Exercise in insulin-dependent diabetes mellitus: the effect of continuous insulin infusion using the subcutaneous, intravenous, and intraperitoneal sites. 634 16

In Microtus arvalis Pallas, new born voles were fostered to ICR mice and supplied with pellets for mice after weaning. A high concentration of glycosuria was shown in about 50% of the voles and continued for over ten weeks. Concentrations of blood glucose and plasma FFA iun glycosuric voles were three or four times as high as those in normal controls. The fermentation ability and pH lowered in the esophageal sac, and comparatively large amount of starch existed in the pyloric stomach of the glycosuric voles. This demonstrated that the dietary starch were tolerably transported to the pyloric stomach without being fermented in the esophageal sac. Glycosuria was also induced in about 50% of the voles supplied with an acidified water (0.02 N HCl, pH 1.7), and the glycosuric voles showed a low pH (1.4-4.2) and lowering of the fermentative ability in esophageal sac. Such an abnormal fermented conditions in the esophageal sac is considered to induce glycosuria in the voles. Glucose tolerance in the diabetic voles which were supplied with pellets for mice lowered considerably with the progress of the disease. On the other hand, plasma insulin levels in the slight diabetic cases rose to eight times as high as normal level, but they lowered considerably with the progress. In the serious cases, the voles fell into complete insulin deficiency. From the above results, the herbivorous Microtus species was considered to be useful as an "animal model" of the dietetic diabetes.
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PMID:[Induction of dietetic diabetes in Microtus arvalis Pallas and its developmental mechanism]. 636 3

In a study of the possible introduction of Japanese field vole (Microtus montebelli ) and Hungarian voles (M. arvalis) as herbivorous experimental animals, the following biological characteristics were investigated: breeding and reproductive performance; bacterial flora and fermentation in the digestive tracts; and nutritional physiology. The animals are polyestrus , show postpartum estrus on the day of parturition, and there is little or no delay in implantation due to lactation, especially in M. arvalis. On examination of vaginal smears, Japanese field vole did not show any definite pattern, whereas most Hungarian voles showed 6- to 18- day cycles. From the esophageal sac of voles fed rations with a high fiber content, cellulolytic bacteria similar to Ruminococcus albus, Ruminococcus flavefaciens , and Bacteroides succinogenes were isolated. More than 1 000 000/g anaerobic bacteria were present in the esophageal sac and the pattern and the types of bacteria resembled those found in the rumen. Gastric fermentation took place in the esophageal sac. The pH and total VFAs were much smaller in the fundic and pyloric regions of the stomach than in the esophageal sac. Acetic and lactic acids were the major fermentation products in the esophageal sac. Following deficiency or lowering of the cellulose decomposing abilities, a decrease of VFAs and an increase in lactic acid production in the esophageal sac were observed. These effects resulted in high glucose, FFA and ketone bodies in the blood, and a higher incidence of glucosuria. Diabetes induced by administrations of drugs such as alloxan, streptozotocin and phloridzin were compared using Microtus and mice. Microtus had low sensitivity to alloxan but high sensitivity to streptozotocin. The influence of monensin on Microtus was also investigated by using diets containing 20 and 80 mg/kg monensin. Diets containing 80 mg/kg monensin led to 50 % mortality in 7 weeks and growth was hindered. Gas production from the esophageal sac contents of voles in the monensin-medicated group was much smaller than that of the non-medicated group. In the monensin group the total VFA concentrations of the esophageal sac contents was decreased.
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PMID:Microtus species as new herbivorous laboratory animals: reproduction; bacterial flora and fermentation in the digestive tracts; and nutritional physiology. 637 75

It has recently been shown that conventionally treated IDDMs are insulin resistant. Using the insulin clamp technique, we studied the influence of metabolic status on the in vivo insulin effect in these patients. Eleven IDDMs, treated conventionally with diet and insulin for 10.7 +/- 5.6 yr, were studied before and after continuous subcutaneous insulin infusion (CSII) treatment (with a portable pump) for 6 mo. We found that conventionally treated diabetic subjects were extremely insulin resistant with regard to peripheral glucose uptake. Glucose uptake, at an insulin concentration of about 80 microU/ml, was 4.3 +/- 2.0 mg/kg X min before treatment compared with 11.5 +/- 4.0 mg/kg X min in normals (P less than 0.01). After pump treatment for 6 mo, metabolic control improved significantly (HbA1c decreased from 8.9 +/- 1.9% to 7.4 +/- 1.2%, P less than 0.01) and, parallel to that, glucose uptake increased about 80% to 7.5 +/- 3.5 mg/kg X min (P less than 0.01). The mean daily plasma FFA level decreased from 0.32 +/- 0.10 mmol/L to 0.21 +/- 0.07 mmol/L (P less than 0.01); this variable was negatively correlated to the glucose clearance rate (r = -0.62, P less than 0.01). There was no statistically significant change in mean daily plasma insulin and plasma growth hormone levels or in 24-h cortisol excretion in the urine (P greater than 0.1). The insulin binding capacity of serum IgG was also unchanged, and there was no significant relationship between this quantity and glucose clearance rates (r = 0.18, P greater than 0.1). We conclude that conventionally treated IDDMs are insulin resistant with regard to peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Sep
PMID:Improved in vivo insulin effect during continuous subcutaneous insulin infusion in patients with IDDM. 638 Nov 79

Diabetes induced by streptozotocin (STR) (55 mg/kg i.v.) in non-fasting, male albino rats is considerably mitigated by adrenalectomy. The timing of the operation is important for the effect of blood glucose. The later the adrenalectomy, the lesser the protection against STR. Plasma insulin in intact, STR-treated rats is significantly lower than in rats that have also been adrenalectomized. Pancreatic insulin in both groups is 10 times lower than in normal controls and adrenalectomized rats. Plasma FFA are distinctly elevated in intact, STR-treated rats. Adrenalectomy in these diabetic animals reduces plasma FFA to levels below those of normal controls. The changes in the glycogen contents of the diaphragm and myocardium of STR-treated rats are reversed by adrenalectomy. The rate of pancreatic insulin degradation might be retarded or the rate of secretion increased. In addition, sensitivity to insulin is exaggerated after adrenalectomy, as is evident from the changes in blood sugar and the glycogen contents of the organs. These changes in the effects of insulin are ascribed to deprivation of adrenal steroids and in particular glucocorticoids. Loss of the adrenal medulla is presumably one of the causes of the changes in plasma FFA.
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PMID:Role of the adrenals in the development of streptozotocin (STR)-induced diabetes in male albino rats. 639 66


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