The effect of extend bar containing uncooked cornstarch on night-time glycemic excursion in subjects with type 2 diabetes

The objective of this study was to determine the effects of ingesting a snack bar containing uncooked cornstarch (Extend Bar, Clinical Products, Limited, Key Biscayne, FL) on nocturnal glycemic excursion in 28 adults (ages 22-78 years) with type 2 diabetes mellitus (mean HbAlc 8.21+/-1.28%). Thirteen subjects were treated with oral agents, eight with a combination of insulin and oral agents, and seven with insulin alone. Subjects ingested the study bar (Extend Bar, containing 30 g of total carbohydrate, including 5 g of uncooked cornstarch, 3 g protein, and 3 g fat) for three evenings followed by a placebo bar for 3 evenings (30 g of total carbohydrate, 3 g protein, and 3 g fat), or vice versa. Pre-snack before bedtime, midnight and before breakfast finger stick blood glucose levels were compared to determine the incidence of hypoglycemia (<60 mg/dl), hyperglycemia (>250 mg/dl), and to calculate any differences in the group's mean blood glucose levels when ingesting the study versus the placebo bar. There were no episodes of hypoglycemia or hyperglycemia. The mean blood glucose levels pre-snack at bedtime were nearly identical (Extend Bar value 117.5+/-45.6 mg/dl; placebo bar value 117.3+/-40.0 mg/dl; P=0.977), and lower at midnight and before breakfast on the Extend Bar nights compared to the placebo bar nights (Extend Bar, midnight value 127.9+/-31.0 mg/dl; placebo bar midnight value 148.2+/-32.1 mg/dl; P=0.0001; Extend Bar breakfast value 114.2+/-15.8 mg/dl; placebo bar breakfast value 158.49+/-30.3 mg/dl; P<0.0001). These data suggest that ingesting Extend Bar containing uncooked cornstarch as the nighttime snack may be an effective strategy to lesson the frequency of nocturnal and morning hyperglycemia in subjects with type 2 diabetes.     

A randomized, blinded trial of uncooked cornstarch to diminish nocturnal hypoglycemia at Diabetes Camp

Objective: To determine if uncooked cornstarch, as part of the evening snack, can avert nocturnal hypoglycemia in type 1 diabetes. Research Design and Methods: Fifty-one campers and counselors at the American Diabetes Association Camp in San Bernardino, CA were randomly assigned to receive 5 g of uncooked cornstarch as part of the 21:00 evening snack vs. a standard snack of equivalent carbohydrate content. Each snack was given for five nights and the participants and medical personnel were blinded as to assignment. Midnight and 07:00 finger stick blood glucose levels were compared with values <60 mg/dl defined as hypoglycemia and values >250 mg/dl defined as hyperglycemia. Results: There were 218 midnight and 222 07:00 values for comparison. There were six episodes of hypoglycemia at midnight and nine episodes of hypoglycemia at 07:00 for the cornstarch snack nights vs. 30 hypoglycemia episodes at midnight and 21 at 07:00 for the standard snack nights (P < 0.001 and < 0.05, respectively). There was no difference in the number of hyperglycemic events at midnight or 07:00 for the cornstarch vs. standard snack nights. At midnight, 12% of campers had hypoglycemia after the cornstarch snack vs. 46% after the standard snack (P < 0.001), and at 07:00, 16% had hypoglycemia after cornstarch vs. 26% after the standard snack (P = 0.327). Conclusions: These data suggest that uncooked cornstarch, as part of the evening snack, can diminish the nighttime and morning hypoglycemia associated with type 1 diabetes, without causing hyperglycemia.     

Predicting nocturnal hypoglycemia in patients with type I diabetes treated with continuous subcutaneous insulin infusion

The incidence of low nocturnal blood glucose values (i.e., less than 65 mg/dl) was assessed in 20 insulin-dependent diabetic patients treated with continuous subcutaneous insulin infusion supported by capillary blood glucose monitoring before each meal and the evening snack. Patients were randomly assigned to a control or experimental group. Both groups followed an identical protocol for the first part of the study (baseline). Patients were instructed to determine capillary blood glucose measurements five times during the night for three consecutive nights. The same procedure was repeated one week later, but this time the subjects in the experimental group were instructed to have an extra snack if capillary blood glucose levels at 10:30 P.M. were 120 mg/dl or less. The control group continued with the usual routine of one evening snack at 9 P.M. At baseline, the incidence of capillary blood glucose values of less than 65 mg/dl was 13 percent. The ingestion of an extra snack at bedtime resulted in the absence of capillary blood glucose values of less than 65 mg/dl in the experimental group, whereas the incidence of capillary blood glucose values of less than 65 mg/dl in the control group remained 13 percent (p = 0.038). The capillary blood glucose concentration at 10:30 P.M. was highly predictive of the risk of nocturnal blood glucose values below 65 mg/dl (p = 0.015) and fasting capillary blood glucose values above 140 mg/dl (p = 0.0001). These data show that nocturnal hypoglycemia may be a considerable problem during continuous subcutaneous insulin infusion therapy even if the basal infusion rate is adjusted in the hospital on the basis of nocturnal blood glucose concentrations. The ingestion of an extra snack at bedtime for capillary blood glucose values below 120 mg/dl has the potential to minimize this risk. The capillary blood glucose concentration at 10:30 P.M. is a significant predictor of nocturnal hypoglycemia.     

Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in intensively treated type 1 diabetes subjects

Abstract . Axelsen M, Wesslau C, Lönnroth P, Arvidsson Lenner R, Smith U (Sahlgrenska University Hospital, Göteborg University, Sweden). Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in intensively treated IDDM subjects. J Intern Med 1999; 245 : 229–36. Objectives. The present study tests two interrelated hypotheses: (1) that bedtime ingestion of uncooked cornstarch exerts a lower and delayed nocturnal blood glucose peak compared with a conventional snack; (2) that bedtime carbohydrate supplement, administered as uncooked cornstarch, prevents nocturnal hypoglycaemia without altering metabolic control in intensively treated type 1 diabetes (IDDM) patients. Design  and subjects. The above hypotheses were tested separately (1) by pooling and analysing data from two overnight studies of comparable groups of patients with non-insulin dependent diabetes mellitus (NIDDM) (14 and 10 patients, respectively), and (2) by a double-blind, randomized 4-week cross-over study in 12 intensively treated IDDM patients. Setting. Sahlgrenska University Hospital, Göteborg, Sweden. Interventions. (1) Ingestion of uncooked cornstarch and wholemeal bread (0.6 g of carbohydrates kg^?1 body weight) and carbohydrate-free placebo at 22.00 h. (2) Intake of uncooked cornstarch (0.3 g kg^?1 body weight) and carbohydrate-free placebo at 23.00 h. Main outcome measures. (1) Nocturnal glucose and insulin levels; (2) frequency of self-estimated hypoglycaemia (blood glucose [BG] levels < 3.0 mmol L^?1) at 03.00 h, HbA_1c and fasting lipids. Results. Bedtime uncooked cornstarch ingestion led to a lower (2.9 ± 0.5 vs. 5.2 ± 0.6 m m , P = 0.01) and delayed (4.3 ± 0.6 vs. 2.0 ± 0.0 h, P < 0.01) BG peak, compared with a conventional snack, in NIDDM patients. Four weeks of bedtime uncooked cornstarch supplement, as compared with placebo, led to a 70% reduction in the frequency of self-estimated hypoglycaemia at 03.00 h (P < 0.05), without affecting HbA1c or fasting lipids in IDDM patients. Conclusions. Uncooked cornstarch, ingested at bedtime, mimicked the nocturnal glucose utilization profile following insulin replacement, with a peak in blood glucose after 4 h. In IDDM patients, bedtime uncooked cornstarch supplement diminished the number of self-estimated hypoglycaemic episodes, without adversely affecting HbA1c and lipid levels. Hence, bedtime uncooked cornstarch ingestion may be feasible to prevent a mid-nocturnal glycaemic decline following insulin replacement in IDDM and, based on the nocturnal blood glucose profile, may also be preferable compared with conventional snacks.     

Benefit of uncooked cornstarch in the management of children with dumping syndrome fed exclusively by gastrostomy

Objective: Children with dumping syndrome fed exclusively by gastrostomy are difficult to manage because liquid diets are given directly into the antrum. The gastric contents are emptied rapidly into the small intestine, with consequent hyperglycemia followed by a delayed hypoglycemia and multiple, often debilitating, symptoms. Uncooked cornstarch is a complex carbohydrate that provides a slow and continuous glucose source and may delay gastric emptying. The objective of this study was to determine the efficacy of uncooked cornstarch in the treatment of these children.
Methods: The medical records of eight children with dumping syndrome fed exclusively by gastrostomy were reviewed. Dumping syndrome was diagnosed if there was consistent symptomatology, rapid gastric emptying, and abnormal glucose measurements after a glucose tolerance test. Enough uncooked cornstarch to match hepatic glucose production for 4 h was added to control hypoglycemia, and the feeding formula was modified to control hyperglycemia.
Results: All patients had debilitating symptoms. Weight z-score on admission was −2.31 ± 0.29. Glucose shifts were controlled in all. There was a significant difference between the maximum (221.3 ± 19.3 mg/dl vs 121.3 ± 6.9 mg/dl;   p < 0.008  ) and minimum serum glucose (47 ± 7.8 mg/dl vs 65.6 ± 4 mg/dl;   p < 0.04  ) before and after uncooked cornstarch. Weight increased from 11.87 ± 1.4 kg to 15.10 ± 2.3 kg (   p = 0.06  ). In seven patients, bolus feedings were successfully administered, and symptoms improved or resolved.
Conclusions: Uncooked cornstarch controlled the glucose shifts, resolved most of the symptoms, allowed bolus feedings, and enhanced weight gain in these children.     

Comparison of breakfast and bedtime administration of insulin glargine in children and adolescents with Type 1 diabetes

OBJECTIVE: The purpose of this study was to evaluate the effect of administration time of insulin glargine (IG) on glycemic control in children and adolescents with Type 1 diabetes. MATERIALS AND METHODS: A total of 31 children and adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime NPH and premeal insulin aspart) were randomized to receive once-daily IG either at breakfast (breakfast group, n=15) or bedtime (bedtime group, n=16) while continuing insulin aspart premeals for 6 months. Blood glucose levels were measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body mass index (BMI), glycosylated hemoglobin (HbA(1c)), and frequency of hypoglycemia in the preceding 3 months were assessed at recruitment, third month and sixth month. RESULTS: The dose of IG, TDD, and fasting blood glucose levels were similar in both groups during the study period. The only significant difference in blood glucose levels between breakfast and bedtime groups was found for dinnertime at 6 months (135+/-26mg/dl versus 161+/-33mg/dl, respectively, p=0.035). In the breakfast group, the mean HbA(1c) level was significantly lower than that of baseline at month 6 (9.4+/-2.5% versus 8.0+/-0.9%, respectively, p=0.022), whereas there was no significant change in the bedtime group (9.2+/-2.1% versus 8.9+/-2.2%, respectively). The frequency of hypoglycemia was lower with IG than NPH (2.7+/-2.8/6 months versus 6.4+/-6.7/6 months, respectively, p=0.008). CONCLUSIONS: Once-daily IG at breakfast in children and adolescents with Type 1 diabetes on intensive therapy is more efficacious than bedtime administration to improve metabolic control. Also, the number of hypoglycaemic events decreased with both breakfast and bedtime administrations of IG.     

Profiles of metabolic control in diabetic children-frequency of asymptomatic nocturnal hypoglycemia

Twenty-four hr glucose and hormonal monitoring was conducted in 34 randomly selected children with insulin dependent diabetes. Asymptomatic nocturnal hypoglycemia was present in 18% (6/34). The nocturnal plasma glucose decline of 20-25 mg/dl/hr reached a mean nadir of 50 mg/dl. The mean rebound hyperglycemia of 300 mg/dl over the subsequent 6.4 hrs. was significantly greater than any glucose excursion in diabetic children with daytime, symptomatic hypoglycemia (n = 5) or in those with non-hypoglycemic profiles (n = 23). Coincident with the nocturnal decline, but preceding the glucose nadir, was a marked release of growth hormone which was significantly greater (p less than .05) than that observed in the other diabetic groups. This release of growth hormone, and the nocturnal hypoglycemia, were reflected in the ratio of awake/sleep mean concentrations of glucose and growth hormone. These data support the speculation that growth hormone release contribute to the hyperglycemic rebound observed. Mean 24 hr growth hormone concentrations varied considerably from patient to patient such that a generalization for growth hormone concentrations in insulin dependent diabetes cannot be made. Asymptomatic nocturnal hypoglycemia is a frequent complication of the therapy of insulin dependent diabetes. Subsequent hyperglycemic rebound (the "Somogyi Effect") is associated with exuberant counterregulatory release of growth hormone. The precise pathophysiological role of this growth hormone release is unclear.     

Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients.

We performed a randomized crossover open comparative study to evaluate the efficacy and safety of voglibose and acarbose in 30 patients with type 2 diabetes who were not well controlled with diet therapy. There was no significant reduction of FBG with either voglibose or acarbose at 4 and 8 weeks after treatment. The 1 h postprandial blood glucose (PPBG) level was significantly decreased from 224.9+/-42.8 to 204.1+/-37.6 (P=0.005) and 206.1+/-38.9 mg/dl (P=0.038) after voglibose therapy at 4 and 8 weeks, respectively. Significant decrease was also obtained after acarbose treatment from 228.3+/-37.4 to 182.7+/-35.5 (P<0.001) and 186.6+/-36.1 mg/dl (P<0.001). The decrease of 1 h PPBG was associated with a significant fall of serum insulin concentration. HbA(1c) levels were also significantly decreased from 7.07+/-1.21 to 6.83+/-1.11 (P=0.017) and 6.79+/-1.33% (P=0.036) after voglibose and 6.98+/-0.98 to 6.70+/-1.04 (P<0.001) and 6.59+/-1.04% (P<0.001) after acarbose at 4 and 8 weeks. In contrast to voglibose, treatment with acarbose significantly decreased the 2 h PPBG at 4 and 8 weeks and the 2 h postprandial serum insulin concentration at 8 weeks. Adverse drug events were more commonly reported in acarbose-treated patients (P<0.05). Increased flatulence was observed in 56.7 and 90% of the patients taking voglibose and acarbose, respectively, while abdominal distention was noted in 10 and 16.7%. Significantly decreased body weights of 0.9 and 0.8 kg were recorded at 8 weeks after voglibose and acarbose therapy, respectively. We conclude that both voglibose (0.2 mg) and acarbose (100 mg) thrice daily significantly decreased HbA(1c), PPBG and postprandial insulin levels. At these dose levels, voglibose was associated with less gastrointestinal side effects and slightly less efficacy for postprandial glucose reduction.     

Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure

A 56-year-old woman with diabetic triopathy, rheumatoid arthritis and chronic renal failure was admitted for severe hypoglycemic coma. Arthralgia had been deteriorating for 6 months. Therefore, 5 mg of prednisolone was administered. Postprandial blood glucose (PPG), however, elevated from 260 to 290 mg/dl, although fasting blood glucose (FBG) levels ranged from 80 to 110 mg/dl. Three months after, 270 mg of nateglinide was given in addition to acarbose. After 2 days, hypoglycemia occurred at 02:00 h. Nateglinide was then decreased to 180 mg (before breakfast and lunch). After 5 days, hypoglycemia re-occurred at 01:00 h. Nateglinide was subsequently decreased to 90 mg before breakfast. The PPG levels ranged from 130 to 150 mg/dl. Hypoglycemia did not occur during the next 2 months. On admission, FBG; 59 mg/dl, fasting immunoreactive insulin; 34 microU/ml, indicated hyperinsulinemic hypoglycemia. We administered 20 g of glucose intravenously, however, hypoglycemia recurred 4 times and 20 g of glucose was then administered. Although the plasma nateglinide level decreased, the nateglinide metabolite, N-[trans-4-(1-hydroxy-1methylethyl)-cyclohexanecarbonyl]-D-phenylalanine levels still had not decreased 29 h after nateglinide administration. Therefore, chronic renal failure appeared to alter the pharmacokinetic parameters of the nateglinide metabolite, which had accumulated by chronic renal failure. The nateglinide metabolite caused severe hypoglycemia in this case.     

Nutritional management of hypoglycemia

PURPOSE: People with type 1 diabetes who follow an intensive management program have an increased risk of hypoglycemia, particularly overnight. New strategies for the nutritional management of hypoglycemia are essential. METHODS: The unique properties of foods that affect blood glucose are reviewed, with special attention to a new medical food bar designed to reduce the incidence of nocturnal hypoglycemia. RESULTS: All carbohydrate-containing foods affect blood glucose, but each causes a different rise in concentration. Consuming a variety of conventional foods with different glycemic indices can help control hypoglycemia. A new medical food bar that provides a sequential triphasic release of glucose from sucrose, protein, and uncooked cornstarch can help control blood glucose levels. CONCLUSIONS: Hypoglycemia can be avoided by consuming foods with varying glycemic indices. A new medical food bar that provides sequential release of glucose into the bloodstream may also help control blood glucose levels.     

Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with beta-cell neoplasms of the pancreas

The effects of calcium on fasting plasma insulin and glucose levels were compared in 16 normal subjects and 11 patients with beta-cell neoplasms of the pancreas. Calcium was administered iv either as a rapid calcium infusion (RCI; 2 mg/kg in 1 min) or as a long calcium infusion (LCI; 12 mg/kg in 3 h). In normal subjects, the RCI produced a rise in mean plasma insulin from 11 +/- 1 (+/- SEM) microU/ml basally to a peak of 18 +/- 2 microU/ml (P less than 0.001). No consistent pattern of change in insulin levels occurred during the LCI, and plasma glucose levels did not change significantly with either test. In the patients with beta-cell neoplasms, the RCI resulted in a rapid increase in mean plasma insulin from 36 +/- 6 microU/ml to a peak level of 312 +/- 67 microU/ml (P less than 0.002). With the LCI, a more gradual rise in insulin from 35 +/- 11 to 92 +/- 36 microU/ml occurred (P less than 0.002). The mean increase in insulin in the patients with beta-cell neoplasms was significantly greater for the RCI than for the LCI (P less than 0.01). Pronounced increments in plasma insulin occurred in all 11 patients after the RCI, but in only 3 of 8 patients during the LCI. Plasma glucose levels declined significantly from 69 +/- 7 to 56 +/- 8 mg/dl during the RCI (P less than 0.05) and from 69 +/- 8 to 49 +/- 7 mg/dl during the LCI (P less than 0.005). Symptomatic hypoglycemia developed in 3 patients during the LCI but did not occur after the RCI. These data indicate that calcium is a more effective insulin secretagogue in patients with beta-cell neoplasms when administered as an RCI than as an LCI, and suggest that the RCI may be a useful test for the diagnosis of insulin-secreting tumors.     

Paradoxical effects of glucose feeding on liver regeneration and survival after partial hepatectomy

Although glucose is regularly administered to patients after partial hepatic resection, its contribution to survival and/or liver regeneration is unclear. To examine this question fed and anesthetized rats underwent 68% or 90% hepatectomy and received either oral 20% glucose solution or tap water (controls) ad lib for 24 h. Survival was compared by life table analysis and the regeneration response measured by 3H-thymidine uptake into liver deoxyribonucleic acid (DNA). Profound hypoglycemia (60 +/- 8 mg/dl) following 90% hepatectomy in controls was corrected by glucose feeding (99 +/- 25 mg/dl) and survival was enhanced (75 +/- 0.09% vs. 42 +/- 0.1%, p less than 0.01). No deaths occurred in the 68% hepatectomy groups wherein untreated hypoglycemia was not as severe (106 +/- 6 mg/dl). However, after 68% hepatectomy glucose adversely affected the regeneration response. We conclude that glucose feeding corrected the life threatening hypoglycemia following 90% hepatectomy. Prophylactic glucose administration after 68% hepatectomy reduced the liver regeneration response. Selective glucose administration to prevent lethal hypoglycemia may provide optimal survival and conditions for regeneration.     

Sodium salicylate augments the plasma adrenocorticotropin and cortisol responses to insulin hypoglycemia in man

To test the hypothesis that prostaglandins attenuate neuroendocrine responses to changes in circulating glucose levels in man, we studied the effects of sodium salicylate (SS), a prostaglandin synthesis inhibitor, on the plasma ACTH and cortisol responses to insulin hypoglycemia. Six normal men were given insulin (0.05 U/kg, iv) on 2 different days during the infusion of either SS (40 mg/min) or saline. Compared to the saline control, SS had no significant effect on either the rate of fall of plasma glucose after insulin or the glucose nadir (mean +/- SEM, 33 +/- 3 vs. 36 +/- 3 mg/dl; P = NS). Peak ACTH levels after insulin were higher during SS compared to those during saline in all six subjects (316 +/- 95 vs. 102 +/- 26 pg/ml; P less than 0.05), and SS had a clear effect to increase both the overall ACTH response (F = 21.3; P less than 0.01, by analysis of variance) and the plasma cortisol response (F = 6.72; P less than 0.05, by analysis of variance). The most striking example of this effect of SS occurred in one subject whose peak plasma ACTH was only 44 pg/ml during saline but reached 750 pg/ml during SS despite an identical fall of plasma glucose to 42 mg/dl. Augmentation of the ACTH and cortisol responses to insulin hypoglycemia may be the result of an alteration by SS of recognition of glucose levels by glucose-sensitive cells of the brain, and effect which could be due to the inhibition of prostaglandin synthesis.     

Physiological concentrations of growth hormone exert insulin-like and insulin antagonistic effects on both hepatic and extrahepatic tissues in man

To determine whether increments in circulating GH concentrations within the physiological range would exert insulin-like as well as insulin-antagonistic actions in man and, if so, whether both actions would occur in hepatic and extrahepatic tissues, normal volunteers (n = 6) were infused with human GH (hGH; 100 ng/kg . min) for 6 h along with somatostatin (100 micrograms/h) to suppress insulin, glucagon, and hGH secretion and also with sufficient insulin (100 microU/kg . min) to maintain a constant plasma insulin level. During the final 2 h, glucose (2 mg/kg . min) was infused. In control studies, saline was infused instead of hGH. Infusion of hGH increased plasma hGH to 35 ng/ml. Plasma glucose decreased to 60 +/- 2 mg/dl compared to 67 +/- 1 mg/dl observed in control studies (P less than 0.05); this greater hypoglycemia was due to both greater suppression of hepatic glucose production (P less than 0.05) and greater augmentation of glucose clearance (P less than 0.05). These insulin-like effects of hGH were no longer evident after 2 h. Subsequently, when glucose was infused, plasma glucose increased to 133 +/- 4 mg/dl compared to the 104 +/- 6 mg/dl observed in control studies (P less than 0.01). This greater hyperglycemia was due to both impaired suppression of hepatic glucose production (P less than 0.001) and decreased glucose clearance (P less than 0.01). These results indicate that physiological increments in plasma hGH cause both insulin-like and insulin-antagonistic effects in man and that these actions occur in hepatic as well as extrahepatic tissues. The insulin-like actions of hGH are transient.     

Hypothermia is critical for survival during prolonged insulin-induced hypoglycemia in rats

Hypothermia is a well-known concomitant of hypoglycemia in mammals. We tested the hypothesis that this hypothermia is an important adaptive response to hypoglycemia in 11 normal Sprague-Dawley rats. Twelve-hour fasted, conscious animals received primed, continuous insulin infusions for up to 8 hours. Plasma glucose was clamped between 30 and 40 mg/dL and core body temperature was monitored continuously during the insulin infusions. Five of the animals were maintained in a room temperature environment (22 to 24 degrees C) during the hypoglycemia; all became hypothermic (mean +/- SE nadir core temperature, 31 +/- 0.5 degrees C). Spontaneous activity was reduced in these animals, but they remained conscious and responsive to external stimuli. All five returned to normal behavior after euglycemia was restored at the end of the insulin infusions. In the remaining six animals, hypothermia was prevented during hypoglycemia by warming of the air in their cages (mean of hourly core temperatures, 37 +/- 0.1 degrees C). None of these animals survived more than 7 hours. The severity of the hypoglycemia was no greater in the euthermic than in the hypothermic group, as judged by the mean of individual nadir plasma glucose levels (25 +/- 1 v 24 +/- 1 mg/dl, respectively) and by the mean number of glucose values per animal that were less than 30 mg/dL (2 +/- 1 v 7 +/- 1). Plasma osmolality did not change significantly in either group during the period of hypoglycemia, suggesting that dehydration was not the cause of death in the euthermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized study comparing blood glucose control and risk of severe hypoglycemia achieved by non-programmable versus programmable external insulin pumps.

OBJECTIVE: To compare a non-programmable and a programmable insulin external pump using regular insulin on glycemic stability, the risk of severe hypoglycemia and metabolic control in type 1 diabetic patients.MATERIAL AND METHODS: Ten type 1 diabetic patients were involved in a randomized, crossover study comparing two periods of 3 months with continuous subcutaneous insulin infusion (CSII) either with a non-programmable insulin pump or a programmable insulin pump. Comparisons were made among mean blood glucose values before and after meals, at bedtime and at 2: 00 a.m.; the risk of severe hypoglycemia assessed by the low blood glucose index (LBGI); and HbA1c.RESULTS: Mean average blood glucose (BG) measurements were significantly lower with the programmable in comparison with the non-programmable insulin pump (respectively 157+/-78 vs. 165+/-79, p=0.034). While postprandial values for BG were not different between the two pumps, the use of the programmable pump resulted in a significant decrease in mean preprandial BG levels (140+/-68 vs. 150+/-73 mg/dl p=0.039). Conversely mean BG level was lower at 2 a.m. with the non-prgrammable pump (125+/-81 vs. 134 +/-93 mg/dl, p=0.02) but with a higher incidence of hypoglycemia. Mean LBGI was comparable with the two pumps (3.1+/-8.6 vs. 2.8+/-6.9, p=0.1). There was a 0.2% decrease in HbA1c during the programmable pump period that did not reach statistical significance (p=0.37).CONCLUSIONS: The present study suggests that programmable external insulin pumps, although more complex and more expensive than non-programmable insulin pumps, significantly reduce fasting glycemia during the day without increasing the risk of severe hypoglycemia and are safer during the night.     

应用动态血糖监测系统评价甘精胰岛素作为基础胰岛素治疗的优越性

采用动态血糖监测系统比较磺脲类药物治疗效果不佳的2型糖尿病患者睡前联合甘精胰岛素或中性鱼精蛋白锌胰岛素（NPH）治疗12周后血糖谱的变化。结果显示，联合甘精胰岛素治疗，在空腹血糖达到同样较好控制的同时，夜间低血糖发生率低，全天血糖曲线波动小。     

Are bedtime nutritional strategies effective in preventing nocturnal hypoglycaemia in patients with type 1 diabetes?

Hypoglycaemia remains the major limiting factor for adequate diabetes control for patients with type 1 diabetes (T1D), especially during the night‐time. Although nutritional strategies for nocturnal hypoglycaemia (NH) prevention are regularly suggested in clinical practice, there is no evidence‐based recommendation for the usefulness and optimal composition of a bedtime snack. The aim of this narrative review was to analyse the current state of knowledge on nutritional strategies to prevent NH in individuals with T1D. A literature search was conducted, using PubMed and Medline (1946 to 2013); 16 studies were retrieved. Overall, the level of evidence was low. Results indicated that a calibrated bedtime snack based on bedtime blood glucose (BG) level could be effective to reduce NH occurrence for patients treated with human or animal insulin (short‐acting combined with lente, ultralente and/or intermediate‐acting insulin), but there is no evidence for patients treated with insulin analogues as part of multiple daily injections or insulin pump regimen. Some evidence suggests that including uncooked cornstarch or alanine in the bedtime snack composition could provide some benefits for the prevention of NH. Individualized recommendations of a bedtime snack intake for patients or situations at high risk for NH (long standing diabetes, hypoglycaemia unawareness, prior physical activity, alcohol consumption, bedtime BG close to hypoglycaemia threshold) appear as a prudent recommendation. On the basis of the available evidence, a bedtime snack cannot be recommended systematically but it might be useful if prescribed in an individualized fashion; further research is needed to evaluate these strategies.     

Effects of somatostatin and oral potassium administration on terbutaline-induced hypokalemia

Terbutaline, a beta 2-adrenergic agonist, has been shown to cause hypokalemia and an increase of plasma glucose and serum insulin concentrations. We considered that terbutaline-induced hypokalemia may be due to the insulin-induced shift of potassium (K+) from the extracellular to the intracellular space. If so, then inhibition of insulin secretion by somatostatin would prevent terbutaline-induced hypokalemia. Further, we wondered whether oral potassium pretreatment could prevent terbutaline-induced hypokalemia. Therefore, 10 healthy volunteers (5 men, 5 women; mean age, 23 yr +/- 3 SD) received either sodium chloride (NaCl) or somatostatin intravenously together with 0.25 mg terbutaline subcutaneously in a double-blind crossover design. On a third test day, they received 39 mval of K+ powder orally before terbutaline injection in an open trial. Terbutaline caused a significant decrease of K+ (from 3.96 +/- 0.08 to 3.3 +/- 0.13 mmol/L +/- SEM; p less than 0.0005), accompanied by a significant increase in plasma glucose (from 83 +/- 3.6 to 101 +/- 4.4 mg/dl +/- SEM; p less than 0.01) and serum insulin concentrations (from 11.7 +/- 0.9 to 19.9 +/- 1.1 microU/ml +/- SEM; p less than 0.001), confirming earlier data. Somatostatin pretreatment inhibited the terbutaline-induced hypokalemia; the small fall of K+ (from 3.7 +/- 0.08 to 3.5 +/- 0.2 mmol/L) was no longer significant. Insulin secretion was completely blocked by somatostatin, leading to an even more pronounced increase of blood glucose. Hypokalemia after terbutaline injection was not prevented by oral potassium pretreatment. In summary, the present findings confirm that terbutaline-induced hypokalemia is associated with increased plasma glucose and insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)