Nocturnal Blood Glucose Profiles in Patients with Type 1 Diabetes Mellitus on Multiple (≥4) Daily Insulin Injection Regimens

The aim of the study was to examine nocturnal blood glucose profiles in Type 1 diabetic patients on multiple (⩾4) daily insulin injections. Nocturnal blood glucose profiles were evaluated in 31 patients collecting blood samples half-hourly from 23.00 till 07.30 h, while they were asleep. Nocturnal episodes of hypoglycaemia (blood glucose <3.0 mmol l⁻¹) occurred in 29 % of these nights; 67 % of episodes were asymptomatic. In the early night (23.00–01.00 h), five episodes occurred with a median duration of 1 h. In the early morning (04.00–07.30 h) seven episodes occurred with a median duration of 3 h. No hypoglycaemia was noted from 01.00 to 04.00 h. Bedtime glucose levels appeared to predict ‘early night’ hypoglycaemia but not ‘early morning’ hypoglycaemia. Fasting glucose levels <5.5 mmol l⁻¹ were indicative of preceding ‘early morning’ hypoglycaemia. There was a large intra-individual variation in nocturnal blood glucose profiles. It is concluded that daily monitoring of bedtime and fasting blood glucose levels may be both more reliable and convenient for the prevention of nocturnal hypoglycaemia than periodic testing of blood glucose at 03.00h as is often advised. Setting a target of >5.5 mmol l⁻¹ for fasting blood glucose may decrease the frequency of nocturnal hypoglycaemia.     

Nocturnal hypoglycemia in type 1 diabetes: an assessment of preventive bedtime treatments

OBJECTIVE: We assessed four putative bedtime treatments in the prevention of nocturnal hypoglycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Plasma glucose concentrations were measured every 15 min from 2200 h through 0700 h in 21 patients with type 1 diabetes (mean +/- sd HbA(1C) = 7.1 +/- 1.0%) on five occasions with, in random sequence, bedtime (2200 h) administration of 1) no treatment, 2) a snack, 3) the snack plus the alpha-glucosidase inhibitor acarbose, 4) an uncooked cornstarch bar, or 5) the beta(2)-adrenergic agonist terbutaline. RESULTS: In the absence of a bedtime treatment, 27% of the measured nocturnal plasma glucose concentrations were less than 70 mg/dl (3.9 mmol/liter) in 12 patients; 16, 6, and 1% were less than 60, less than 50, and less than 40 mg/dl (3.3, 2.8, and 2.2 mmol/liter), respectively. Neither the snack (without or with acarbose) nor cornstarch raised the mean nadir nocturnal glucose concentration or reduced the number of low glucose levels or the number of patients with low levels. Terbutaline raised the mean nadir nocturnal glucose concentration (mean +/- se, 127 +/- 11 vs. 75 +/- 9 mg/dl; P < 0.001), eliminated glucose levels less than 50 mg/dl (P = 0.038), reduced levels less than 60 mg/dl (P = 0.005) to one, and reduced levels less than 70 mg/dl (P = 0.001) to five (four at 2215 h, one at 2230 h). However, it also raised glucose levels the following morning. CONCLUSIONS: Nocturnal hypoglycemia is common in aggressively treated type 1 diabetes. Bedtime administration of a conventional snack or of uncooked cornstarch does not prevent it. That of terbutaline prevents nocturnal hypoglycemia but causes hyperglycemia the following morning. The efficacy of a lower dose of terbutaline remains to be determined.     

Nocturnal hypoglycaemia in Type 1 diabetic patients,assessed with continuous glucose monitoring: frequency,duration and associations

Aims We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple‐injection therapy (MIT) using a continuous subcutaneous glucose sensor. Methods A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA_1c 7.8 ± 0.9%) and 33 patients on MIT (HbA_1c 8.7 ± 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA_1c, diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Results Nocturnal hypoglycaemia ≤ 3.9 mmol/l occurred in 33.3% of both the CSII‐ (8/24) and MIT‐treated patients (11/33). Mean (± sd ; median, interquartile range) duration of hypoglycaemia ≤ 3.9 mmol/l was 78 (± 76; 57, 23–120) min per night for the CSII‐ and 98 (± 80; 81, 32–158) min per night for the MIT‐treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Conclusions Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.     

Biochemical evidence for the requirement of continuous glucose therapy in young adults with type 1 glycogen storage disease

Summary To determine whether patients with GSD-1 need nocturnal glucose therapy after completing physical growth and development, studies were performed on two consecutive nights. On the first night uncooked cornstarch (UCS) was given at the calculated glucose production rate at 21:00 h and 02:00 h. On the second night UCS was given at 21:00 h but omitted at 02:00 h. Six GSD-1 patients, aged 17.2–20.9 years, previously treated with continuous glucose therapy were studied. Measurements were made of plasma glucose (PG), serum insulin, growth hormone, cortisol, plasma glucagon (n=4), and blood lactate at 30–60-min intervals. Serum uric acid, cholesterol, and triglycerides were measured at 21:00 h and 07:00 h, and serum FFA at 21:00 h, 02:00 h and 07:00 h on the first night and immediately before treatment for hypoglycaemia on the second night.For five hours after UCS at 21:00 h, mean PG, serum insulin and blood lactate concentrations were similar on the two nights. With UCS at 02:00 h, mean PG concentrations were 4.1 mmol/L from 02:00 to 07:00 h. Without UCS at 02:00 h, in all subjects PG concentrations fell to <2.5 mmol/L after 6.5–8.5 h and mean blood lactate concentration increased to 7.4±3.0 mmol/L.Young adults with GSD-1 developed hypoglycaemia and hyperlactataemia after a relatively brief period without exogenous glucose and, therefore, need to continue nocturnal glucose therapy to prevent fasting hypoglycaemia.     

A novel starch for the treatment of glycogen storage diseases

Summary Objective: To determine whether a new starch offers better short-term metabolic control than uncooked cornstarch in patients with glycogen storage diseases (GSDs). Study design: A short-term double-blind cross-over pilot study comparing uncooked physically modified cornstarch (WMHM20) with uncooked cornstarch in patients with GSD types Ia, Ib and III. Twenty-one patients (ages 3–47, 9 female) were given 2 g/kg cornstarch or WMHM20 mixed in water. Blood glucose, lactate and insulin, and breath hydrogen and ¹³CO₂ enrichment were measured, at baseline and after each load. The hourly biochemical evaluations terminated when blood glucose was ≤3.0 mmol/L, when the study period had lasted 10 h or when the patient wished to end the test. The alternative starch was administered under similar trial conditions a median of 10 days later. Results: The median starch load duration was 9 h for WMHM20 versus 7 h for cornstarch. Glucose decreased more slowly (p = 0.05) and lactate was suppressed faster (p = 0.17) for WMHM20 compared with cornstarch. Peak hydrogen excretion was increased (p = 0.05) when cornstarch was taken. Conclusion: These data indicate longer duration of euglycaemia and better short-term metabolic control in the majority of GSD patients with WMHM20 compared to cornstarch. Competing interests: None declared References to electronic databases: Glycogen storage disease I, OMIM 232200. Glycogen storage disease III, OMIM 232400. Glucose-6-phosphatase, EC 3.1.3.9. Amylo-1,6-glucosidase, EC 3.2.1.33. Oligo-1,4–1,4-glucanotransferase, EC 2.4.1.25     

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM

Summary In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean ± SEM): 16.1 ± 3.1 vs 23.6 ± 3.3) episodes during the last 6 weeks of treatment, p = 0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA_1c 7.2 ± 0.2 vs 7.1 ± 0.2 %, p = 0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study. [Diabetologia (1998) 41: 322–329] Received: 21 July 1997 and in revised form: 7 October 1997     

床边血糖监测系统监测睡前血糖预测住院2型糖尿病患者夜间低血糖发生情况的观察

目的 利用床边血糖监测系统回顾性分析住院T2DM患者睡前血糖与夜间低血糖的主要特点及危险因素. 方法 收集2008年1月至2011年12月接受稳步医院用（SureStep Flexx）床边血糖管理系统连续监测睡前及夜间血糖的2505例T2DM患者共14827次血糖数据行回顾性分析,探讨睡前血糖与夜间低血糖的关系. 结果 （1）夜间低血糖发生率10.8％（271/2505）,总夜间低血糖事件393次,其中严重低血糖发生率15.3％（60/393）,轻度低血糖84.7％（333/393）.（2）睡前血糖＜9.0 mmol/L时,预测夜间低血糖敏感性57.7％,特异性62.3％.（3）男性、≥60岁、胰岛素治疗且睡前血糖＜9.0mmol/L的住院T2DM患者,夜间低血糖发生风险升高（P＜0.05）. 结论 住院T2DM患者睡前血糖＜9.0 mmol/L时,夜间低血糖发生风险升高,应重视睡前血糖监测,预防夜间低血糖发生.     

Incidence of Nocturnal Hypoglycaemia in Insulin-dependent Diabetic Patients on Intensive Therapy

ABSTRACT The frequency of nocturnal hypoglycaemia, i.e. blood glucose concentration (BG) <3.0 mmol/l, was evaluated in consecutively selected insulin-dependent patients on multiple insulin injections (MII), n =23, or continuous subcutaneous insulin infusions (CSII), n =25. Blood was sampled hourly from 23.00 to 07.00. Seven patients (30%) on MII had at least one BG <3.0 mmol/l during the night. Eleven patients (44%) on CSII had hypoglycaemia (NS). The total number of BGs <3.0 mmol/l was higher on CSII, 42 of 225, versus 16 of 207 on MII (p<0.025). The duration of hypoglycaemia was 2 hours (range 1–6) on MII and 4 hours (range 1–7) on CSII with a maximal prevalence at 4 hours and between 5 and 7 hours, respectively (p=<0.05). The frequency of nocturnal hypoglycaemia is high in patients on intensified insulin regimens. Nocturnal hypoglycaemia occurs later in the night and is of longer duration on CSII than on MIL HbA_1c, BG before bedtime and in the morning might be useful in the evaluation of nocturnal hypoglycaemia.     

Sitagliptin improves beta‐cell function in patients with acute coronary syndromes and newly diagnosed glucose abnormalities–the BEGAMI study

Background

Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta‐cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase‐4 inhibitor initiated soon after a coronary event improves beta‐cell function.

Methods

Acute coronary syndromeACS patients with IGT or T2DM (n = 71), screened by oral glucose tolerance test (OGTT) 4–23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg (n = 34) or placebo (n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose‐lowering agents other than the study drug. The study end‐point was beta‐cell function assessed using the insulinogenic index (IGI = ΔInsulin₃₀/ΔGlucose₃₀), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test.

Results

The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol^?1 and 1394 vs. 1106 pmol L^?1 min^?1 respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group (P = 0.013) and AIRg was 1909 and 1043 pmol L^?1 min^?1 (P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L^?1 in sitagliptin‐treated patients and 6.0 mmol L^?1 in those who received placebo compared with 5.8 and 5.9 mmol L^?1 respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin‐treated patients compared with the placebo group (P = 0.003). Sitagliptin was well tolerated.

Conclusion

Sitagliptin improved beta‐cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.

     

Nocturnal hypoglycaemia in IDDM patients younger than 18 years

The present multicentre study was undertaken to assess the prevalence of nocturnal hypoglycaemia and its determining factors in 117 diabetic children and adolescents, aged 2–18 years and diabetes duration >1 year in Spain. Each child made 3 measurements of blood glucose (BG) at home at night (between 0000 h and 0600 h) on nine separate nights. A hypoglycaemic event occurred in 12–14 % of children in any one night. This is lower than rates for nocturnal hypoglycaemia reported in literature, perhaps because of relatively late mealtimes and different meal content, in Spanish children. Children aged <7 years were at higher risk of nocturnal hypoglycaemia than older children (p < 0.05). Mean HBA_1c from the year before the study and mean HbA_1c measured during the closest time to the study were significantly lower in those with nocturnal hypoglycaemia (p < 0.0001). Blood glucose concentrations 2 h before hypoglycaemia did not predict nocturnal hypoglycaemia. The occurrence of low or very low blood glucose concentrations before breakfast was related to a higher risk for nocturnal hypoglycaemia (χ² 22.97; p < 0.001). No previous symptoms were detectable in 89 % of cases. © 1997 John Wiley & Sons, Ltd.     

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.     

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.     

Altered ventricular repolarization during hypoglycaemia in patients with diabetes

There is circumstantial evidence implicating hypoglycaemia in the sudden overnight death of young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM), the mechanism of which is unknown. We have investigated the effects of hypoglycaemia on the electrocardiogram in 15 patients with diabetes (8 with IDDM and 7 with NIDDM) using a high resolution computer-based system. Patients were randomized to either 2 h of euglycaemia or hypoglycaemia (at around 3 mmol l⁻¹ ) during the afternoon, using hyperinsulinaemic glucose clamps, the two visits separated by a period of at least 4 weeks. Corrected QT interval (QTc), plasma potassium, and adrenaline were measured at baseline and at 0, 60, and 120 min. The degree of QTc lengthening (from baseline) during clamped hypoglycaemia was greater compared to the euglycaemic control period in patients with IDDM (median{range} at 60 min, 156{8 to 258 } vs 6{−3 to 28} ms, p <0.02) and NIDDM (120 min, 128{16 to 166} vs 4{ −3 to 169} ms, p <0.05). The fall in plasma potassium was greater during clamped hypoglycaemia compared to euglycaemia in those with NIDDM ( p <0.03) but not with those with IDDM ( p >0.06). The rise in plasma adrenaline was greater during clamped hypoglycaemia in both groups (IDDM p <0.02, NIDDM p <0.02) and there was a strong relationship between the rise in adrenaline and increase in QTc ( r = 0.73, p <0.0001).These data demonstrate alteration of ventricular repolarization with lengthening of the QT interval during hypoglycaemia and suggest a possible mechanism by which hypoglycaemia could cause ventricular arrhythmias. © 1997 by John Wiley & Sons, Ltd.     

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.     

Further evidence for a high incidence of nocturnal hypoglycaemia in IDDM: no effect of dose for dose transfer between human and porcine insulins

We tested the hypothesis that transfer from porcine to human insulin causes a fall in nocturnal blood glucose and an increase in the frequency of hypoglycaemic episodes. Twenty IDDM patients (age 19–55, duration 3–36 years) used Velosulin and Insulatard twice daily for 12 weeks, double-blinded to species (human (H) or porcine (P)) in a randomized crossover study. Species was changed after 4 weeks’ run-in and 4 weeks later, with insulin doses unchanged on transfer. Ten patients underwent each sequence (H/P/H or P/H/P) and were admitted on the first and eighth night after transfer for hourly blood glucose measurement (22.00–07.00). Biochemical hypoglycaemia (<3.5 mmol l⁻¹) was observed on 39 of the 80 patient-nights studied (48.75 %). The number of episodes were similar during each night (H1 8, H8 10, P1 10, P8 11, p = 0.83). Total reported symptomatic episodes (H 51 vs P 73, p = 0.85), total HbA₁ (H 9.8 ± 0.3 %, P 10.0 ± 0.3 %, p = 0.32) and daily insulin doses (H 0.63 ± 0.04 units kg⁻¹ day⁻¹ vs P 0.63 ± 0.05 units kg⁻¹ day⁻¹, p = 0.54) were not different. Despite an apparent fall in blood glucose levels from night 1 to 8 on transfer to human (AUC 82.3 ± 7.8 vs 61.4 ± 5.3 mmol.h l⁻¹, p < 0.05) but not porcine insulin (AUC 70.7 ± 7.2 vs 70.1 ± 7.5 mmol.h l⁻¹, p = 0.74), there was no difference when all 4 nights were considered together (p = 0.30). We conclude that dose for dose transfer to human insulin does not increase numbers of episodes of nocturnal or reported hypoglycaemia. © 1997 by John Wiley & Sons, Ltd.     

Long-term comparison of human insulin analogue B10Asp and soluble human insulin in IDDM patients on a basal/bolus insulin regimen

Summary Recombinant DNA technology allows the production of insulin analogues with faster absorption rates from subcutaneous tissue as compared to soluble human insulin. The human insulin analogue B10Asp (mono/dimeric) is absorbed twice as fast as soluble human insulin (hexameric). A double blind, randomised crossover study with a 1-month run-in period and two 2-month treatment periods was performed in 21 male insulin-dependent diabetic (IDDM) patients aged 18–40 years in order to compare the metabolic control obtained with equimolar doses of the analogue B10Asp vs soluble human insulin (Actrapid) given as mealtime insulin and intermediate acting isophane insulin (Protaphane) at bedtime. At the end of each 2-month study period, the patients were admitted to the metabolic ward. We found significantly higher plasma insulin/analogue levels after breakfast, lunch and dinner with B10Asp as compared to Actrapid (p<0.05). The plasma insulin/analogue levels were significantly lower before lunch and dinner with B10Asp as compared to Actrapid (p<0.05). Also, the plasma insulin/analogue level tended to be lower at bedtime when comparing B10Asp to Actrapid. The 24-h blood glucose profiles showed identical fasting blood glucose, significantly lower blood glucose after breakfast with the analogue (p<0.05), no differences in blood glucose after lunch and dinner but a significantly higher blood glucose at midnight using the analogue (p<0.05). The overall 24-h mean blood glucose concentrations, the daily insulin dose, HbA_1c, diet, home blood glucose monitoring and frequency of hypoglycaemia were almost identical in the two treatment periods. In conclusion, the overall glycaemic control remained unchanged and quite good when Actrapid was exchanged dose for dose with the insulin analogue B10Asp in IDDM patients treated with a basal bolus regime.Abbreviations IDDM Insulin-dependent diabetes mellitus - RIA radioimmunoassay - IGF-I insulin-like growth factor-I     

Less weight gain and hypoglycaemia with once‐daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight Type 2 diabetes patients—The PREDICTIVE™ BMI clinical trial1

Objective To assess weight change when once‐daily insulin detemir (detemir) or neutral protamine Hagedorn insulin (NPH) are used in already overweight Type 2 diabetes patients requiring intensified insulin therapy. Research design and methods This 26‐week randomized, controlled trial included adults with Type 2 diabetes [glycated haemoglobin (HbA_1c) 7.5–11.0%, body mass index (BMI) 25–40 kg/m²] who had received two daily doses of insulin (at least one a premix) for ≥ 3 months. Subjects received either detemir (n = 125) or NPH (n = 146) once daily in the evening and insulin aspart at main meals. Concomitant treatment with metformin was allowed. Basal insulin was titrated to a pre‐breakfast plasma glucose target of 6.1 mmol/l without unacceptable hypoglycaemia. Insulin aspart was also titrated (target, postprandial glucose ≤ 10.0 mmol/l without unacceptable hypoglycaemia). Results At 26 weeks, weight had increased significantly less with detemir (0.4 kg) than with NPH (1.9 kg; difference 1.5 kg, P < 0.0001). BMI increase was also less with detemir than with NPH (difference 0.6 kg/m², P < 0.0001). HbA_1c decreased from 8.9 to 7.8% (detemir) and from 8.8 to 7.8% (NPH; not significant for between‐treatment difference). Incidence of hypoglycaemia was lower with detemir [relative risks 0.62 (all events) and 0.43 (nocturnal); P < 0.0001 for both]. Conclusions PREDICTIVE? BMI was the first study to examine the effect of once‐daily detemir with weight as the primary endpoint in a large population of overweight Type 2 diabetes patients. Use of once‐daily detemir for intensification of insulin therapy resulted in less weight gain, less hypoglycaemia and equivalent glycaemic control compared with NPH.     

Effects of C-peptide on insulin-induced hypoglycaemia and its counterregulatory responses in IDDM patients

Recent studies indicate that C-peptide, when given to patients with insulin-dependent (Type 1) diabetes mellitus (IDDM), exerts significant effects on microvascular and neuronal functions. Adjuvant therapy with C-peptide has been advocated in the treatment of IDDM patients. Since endogenous insulin secretion is believed to be of importance for the alpha-cell function, we addressed the issue whether C-peptide given acutely interferes with the responses to hypoglycaemia. Seven IDDM patients were randomly exposed to hypoglycaemia with and without exogenous C-peptide. Insulin and and C-peptide were given intravenously in equimolar amounts for 3 hours. The decrease of blood glucose was faster and more pronounced during C-peptide infusion, yielding a significantly lower AUC 0–180 min of blood glucose (38.5 ± 1.6 vs 44.4 ± 2.2 mmol l⁻¹ h⁻¹ ; p = 0.032). No difference between the two experiments was found concerning glucagon when the AUC, Δ-values or levels at separate points of time were calculated. In conclusion, the main finding of this study was that exogenous C-peptide, given acutely, gave rise to a more rapid onset of hypoglycaemia yielding no detectable differences with respect to the response of glucagon and other counterregulatory hormones. © 1997 by John Wiley & Sons, Ltd.     

Metabolic characteristics of subjects with normal glucose tolerance and 1-h hyperglycaemia

Objective Nondiabetic subjects with a 1‐h plasma glucose ≥ 11·1 mmol/l during an oral glucose tolerance test (OGTT) drew our attention to their somewhat confusing status and relative frequency among Chinese patients. The aim of this study was to clarify the metabolic characteristics of these subjects. Design and patients A total of 2549 Chinese subjects were included in this study. Based on results of OGTT, these subjects were classified into three groups: normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes mellitus (DM). Then, according to the level of 1‐h plasma glucose, the NGT and IGR groups were subclassified, respectively, as: NGT without 1‐h hyperglycaemia (NGTN), NGT with hyperglycaemia at 1 h (NGT1H), IGR without 1‐h hyperglycaemia (IGRN), and IGR with hyperglycaemia at 1 h (IGR1H). Results After adjustments for age and gender, the insulinogenic index (IGI) of NGT1H and IGR1H was found to be lower than for those with NGTN and of IGRN, respectively (P < 0·05). No statistical differences, however, were found in oral glucose insulin sensitivity (OGIS) between either of the 1‐h hyperglycaemic groups or of the corresponding NGTN or IGRN groups. Homeostasis model assessment for β‐cell function (HOMA‐B) of NGT1H was lower than that of NGTN (P < 0·05), while IGRN and IGR1H showed no difference. No differences in homeostasis model assessment for insulin resistance (HOMA‐IR) were found among NGTN, NGT1H, IGRN and IGR1H groups. The levels of triglycerides (TG) were not significantly different among NGT1H, IGRN and IGR1H, while TG in these groups were significantly higher than in NGTN (P < 0·05). LDL‐C was significantly higher and HDL significantly lower in NGT1H than in all other groups (P < 0·05).The IGR group was also subclassified as: isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined glucose intolerance (CGI). The IGI of the NGT1H group was similar to the IGI that of combined glucose intolerance group but lower than those of IFG and IGT (P < 0·05).The OGIS of the NGT1H group was the highest among all groups (P < 0·05). HOMA‐B of IGT and NGT1H were higher than that of IFG (P < 0·05). There was no difference among all groups in HOMA‐IR. Plasma lipid levels were not significantly different between NGT1H and any other group. Conclusions Chinese NGT subjects with a 1‐h plasma glucose ≥ 11·1 mmol/l are characterized by metabolic abnormalities, which may be caused by the impairment of early insulin release rather than aggravated insulin resistance.     

Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: A controlled study in normal subjects

Background & Aims: Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily. Methods: Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg. Results: Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0.05, ranitidine vs. placebo). Conclusions: Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.GASTROENTEROLOGY 1998;115:1335-1339