Correction to: Hypoglycemia, Malnutrition and Body Composition.

The original version of this chapter was inadvertently published with a subtitle which was a duplication of the chapter title.

Hypoglycemia, Malnutrition and Body Composition.

Hypoglycemia is one of the most significant factors to affect prognosis, and is detrimental to patients regardless of diabetes mellitus (DM) status. The classical paradigms dictate that hypoglycemia is a result of overtreatment with glucose lowering agents (iatrogenic hypoglycemia), or, as among patients without DM, this condition is attributed to disease severity. New information shows that hypoglycemia occurs among patients that have a tendency for it. Incident hypoglycemia is very prevalent in the hospital setting, occurring in 1:6 patients with DM and in 1:17 patients without DM (Leibovitz E, Khanimov I, Wainstein J, Boaz M; Diabetes Metab Syndr Clin Res Rev. 13:222-226, 2019).One of the major factors associated with incidence of hypoglycemia is the nutritional status on hospital admission and during the hospitalization. Assessment of nutritional status using questionnaires and biomarkers might be helpful in determining risk of hypoglycemia. Moreover, administration of oral nutritional supplements was shown to decrease this risk.It is also well known that a high burden of comorbidities is associated with an increased risk of hypoglycemia. For example, kidney disease, whether acute or chronic, was shown to increase the risk for hypoglycemia, as well as some endocrine disorders.In this review we elaborate on specific findings that are characteristic of patients at risk for developing hypoglycemia, as well as treatment aimed at preventing its occurrence.

Reduction of serum albumin in non-critically ill patients during hospitalization is associated with incident hypoglycaemia.

AIM: Our study looked at the association between changes in serum albumin (SA) levels during hospitalization and incidence of hypoglycaemia among non-critically ill patients. METHODS: Included were patients discharged from internal medicine units with hospital stays ≤ 14 days. Patients were allocated to three groups: (1) admission SA > 3.5 g/dL with no decrease during hospitalization; (2) admission SA < 3.5 g/dL with no decrease during hospitalization; and (3) decrease in SA regardless of admission SA level. Incident hypoglycaemia (glucose ≤ 70 mg/dL) was predicted by applying regression analysis, using hypoglycaemia as a dependent variable. Mortality studies were performed using Cox regression. RESULTS: Included were 7718 patients (mean age 71.8 ± 17.4 years, 49.9% males, 27.1% with diabetes). Of these patients, 12.7% had at least one documented hypoglycaemia episode during hospitalization. Patients with decreases in SA levels during hospitalization (group 3) had higher rates of incident hypoglycaemia compared with patients in groups 1 and 2 (21.0% vs. 6.0% and 16.3%, respectively; P < 0.001 for both). Results remained significant after controlling for admission SA. Strong negative correlations were observed between SA and serum osmolarity (r = -0.204, P < 0.0001) and, separately, between changes in SA with changes in serum osmolarity (r = -0.157, P < 0.001), indicating that SA changes were not due to haemodilution. Overall 1-year mortality was 16.7%, and Cox regression analysis showed an increased 1-year mortality in patients in group 3 (27.9%) compared with those in groups 1 and 2 (15.2% and 13.8%, respectively). CONCLUSION: Changes in SA during hospitalization are associated with an increased risk of hypoglycaemia during hospitalization of non-critically ill patients.

Association of albumin and cholesterol levels with incidence of hypoglycaemia in people admitted to general internal medicine units.

AIM: To study the association between serum albumin and cholesterol levels at hospital admission and incident hypoglycaemia among people admitted to internal medicine units. METHODS: In this cross-sectional analysis, we examined the electronic medical records of people hospitalized in internal medicine departments. Data extracted included all glucose measurements as well as serum albumin and cholesterol, which were measured upon admission. A hypoglycaemia event was recorded for a given person if at least one glucose measurement of ≤ 3.9 mmol/l was recorded during the hospital stay. Regression analysis was used to determine which clinical measures predict hypoglycaemia. RESULTS: During the acquisition period, 45 224 people (mean age 68.9 ± 17.8 years, 49.4% male, 21.1% diabetes mellitus) were discharged from internal medicine units. Hypoglycaemia was documented in 7.5% of these individuals (15.4% of people with diabetes vs. 5.5% of those without; P < 0.001). Logistic regression showed that both serum albumin [odds ratio (OR) 0.908, 95% confidence interval (CI) 0.896-0.919; P < 0.001) and cholesterol (OR 0.938, 95% CI 0.896-0.981; P = 0.005] were significantly associated with incident hypoglycaemia. Results remained significant even after controlling for age, sex, average glucose during hospitalization, length of hospital stay, acute infection upon admission, diabetes status, haemoglobin, white blood cell count and C-reactive levels. A combination of hypoalbuminaemia (< 35 g/l) and hypocholesterolaemia (< 3.37 mmol/l) upon admission greatly increased the risk of incident hypoglycaemia (OR 2.544, 95% CI 2.096-3.088; P < 0.001). CONCLUSION: Hypoalbuminaemia and hypocholesterolaemia predict incident hypoglycaemia in the hospital setting among people with and without diabetes mellitus.

Effect of short- and long-term diabetes control on in-hospital and one year mortality rates in hospitalized patients with diabetic foot.

INTRODUCTION: It remains unclear whether diabetic patients with diabetic foot complications benefit from strict glycemic control during hospitalization The present study investigates the effect of short- and long-term diabetes control on hospital outcomes including: in-hospital and one year mortality rates, length of hospital stay and the rate of repeated admissions. METHODS: Type 2 diabetic patients (n = 341) were hospitalized for diabetic foot complications at Wolfson Medical Center over a 5 year period (2008-2012). The adequate short-term glycemic control was defined as average glucose levels between 110 and 180 mg/dL. HbA1c values below 7% were defined as adequate long-term glycemic control. RESULTS: The average glucose levels during hospitalization were 179 ±â€¯45 mg/dL and 40% of the measurements were between 110 and 180 mg/dL. Mean admission HBA1c levels were 8.43% ±â€¯2.26%, and 31% of the values were below 7%. The mean length of hospital stay was 24.3 ±â€¯22.6 days, 15.0% of the patients needed surgical intervention during admission, the in-hospital mortality rate was 10.3%, and the rate of 1-year readmission was 25.1%. Adequate diabetes control during hospitalization was not significantly associated with reduced in-hospital mortality (hazard ratio, 0.454, 95% confidence interval 0.186-1.103, p = 0.081). However, adequate diabetes control during hospitalization lead to significantly decreased one year mortality (hazard ratio, 0.269, 95% confidence interval 0.707-0.101, p = 0.009). Adequate diabetes control during hospitalization did not affect the length of hospital stay or the rate of repeated admission. CONCLUSIONS: Improved glucose control during hospital admission (levels between 110 and 180 mg/dL) was associated with reduction of one year mortality.

Adaptability of structured forms for CSII initiation in patients with type 2 diabetes the Getting2Goal(SM) concept.

BACKGROUND: The goal is to assess the usability and satisfaction of implementing the Getting2Goal(SM) protocol by physicians transitioning patients with type 2 diabetes (T2DM) from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII). METHODS: T2DM patients from three diabetes clinics were switched from MDI to CSII. Physicians used the Getting2Goal type 2 pumping protocol to prescribe and manage insulin pump therapy for T2DM. Surveys were conducted in which the physicians rated their feedback related to acceptability of the Getting2Goal on a 5-point Likert scale. RESULTS: 17 patients with T2DM were switched from MDI to CSII treatment. Mean (±standard deviation) age was 61.2 ± 7.7 (46-77) years, weight was 91.4 ± 21 (66-147) kg, BMI was 31.9 ± 7.6, A1C was 9.2 ± 1.4 % (7.2-12.3) and TDD on MDI was 109.1 ± 53.1 units. Surveys completed by physicians indicated Getting2Goal type 2 pumping protocol to be more efficient, time saving, and structured compared to their current processes. In addition, the primarily prescribed TDD on pump was 98.1 ± 50.0 units and the TDD at first download was 81.4 ± 36.4 units, representing a 25.4 % reduction in TDD At first download. The percentage of all blood glucose readings below 70 mg/dL was also very low. CONCLUSIONS: The data indicate Getting2Goal materials as a standard approach that is simple and efficient to initiate pump therapy for T2DM. At the same time, it is safe and a useful tool for physicians that are starting to prescribe pump therapy for T2DM.

Hyperglycaemia in patients with no history of diabetes presenting to Internal Medicine Departments.

AIMS: Stress hyperglycaemia during hospitalisation may be the first sign of diabetes mellitus (DM). Most hospitals routinely measure blood glucose, which may enable early diagnosis. This study measured the prevalence of hyperglycaemia in hospitalised adults with no history of diabetes, and whether the discharge summary recommended work-up. METHODS: Files with at least one random blood glucose (RBG) sample were included and reviewed for specific discharge recommendations concerning elevated blood glucose. Hyperglycaemia was defined as serum glucose > 200 mg/dl. Length of stay, in-hospital mortality and 3-year mortality were examined. RESULTS: Among 5274 discharged patients, 1479 had DM. They were older and had a higher incidence of cerebrovascular risk factors. Among 3714 patients without known DM, 211 (5.7%) had at least one RBG > 200 mg/dl. Of these patients, 31 died and 24 left against medical advice. Of the remaining 156, 25(16%) files included instructions to the family physician. These patients were younger, more overweight and less frequently diagnosed with dementia or other mental illness. Patients with RBG > 200 mg/dl had prolonged hospital stay (6.5 ± 5.3 vs. 4.0 ± 4.8; p < 0.001). In-hospital mortality and 3-year mortality were increased by 5.1 and 1.89, respectively (p < 0.001 for both parameters) compared to those without RBG ≤ 200 mg/dl. RBG > 200 mg/dl emerged as a significant, independent predictor of prolonged hospital stay and death. CONCLUSIONS: Random blood glucose > 200 mg/dl is common in medical departments and is associated with increased in-hospital and 3-year out-hospital mortality.

Inpatient hyperglycaemia improvement quality program.

BACKGROUND: Poorly controlled hyperglycaemia is associated with increased morbidity and mortality in hospitalised patients. Based on the view that hospitalisation provides a window of opportunity to improve patient quality of care and health status, a comprehensive program for treating hospitalised diabetic patients was initiated. This study assessed the effectiveness of the Inpatient Hyperglycaemia Improvement Quality Program (IHIQP) over a 4-year period. METHODS: Pre-test post-test design. In the pre-intervention period (August-December 2007), an institution-wide blood glucose monitoring system was introduced in August 2007. The remaining program components were introduced in January 2008, including implementing a hospital care protocol based on the 2007 American Diabetes Association Standards, a multidisciplinary team that participates in patient care and arranges continuing care after discharge and comprehensive patient education prior to discharge. Program results from January 2008 through October 2011 were evaluated. RESULTS: During follow-up, more than 600,000 blood glucose tests were performed. Blood glucose values declined from 196.4 ± 98.4 mg/dl pre-IHIQP (August-December 2007) to 174.5 ± 82.0 mg/dl post-IHIQP (January-October 2011) (p < 0.0001). Prevalence of glucose values lower than 60 mg/dl declined from 2% to 1.3% (p < 0.004). Prevalence of glucose values ≥ 300 mg/dl declined from 13.6% to 8.4% (p < 0.0001). Concomitantly, the proportion of in-target values of 80-180 mg/dl increased from 47.7% to 58.1% (p < 0.0001). CONCLUSION: This in-patient hyperglycaemia quality improvement program led to improvements in-patient glycaemic control, which continued over time. The effect of this improvement on in-patient mortality and morbidity needs additional follow-up.

Opinion and knowledge among hospital medical staff regarding diagnosis of diabetes and proper usage of a specific test tube for glucose analysis.

BACKGROUND: Accuracy of blood sugar values, as examined by glucose analysis, has significant importance on the diagnosis of diabetes and follow up of diabetes treatment. Usage of a designated test tube significantly improves the accuracy of measurement. Knowledge of the medical staff is a major determinant in the current usage of such a technology. The aim of the study was to assess the level of knowledge exhibited by medical staff in the diabetes field and specifically for the usage of a designated tube to test blood glucose level. METHODS: A prospective study. The staff of the internal and surgical departments and outpatient clinics at the Wolfson Medical Center completed a questionnaire that assessed the level of knowledge about the designated glucose test tube, other randomly used test tubes, the parameters that influence the blood glucose values in a non-designated tube and the diagnosis of diabetes. RESULTS: A number of 160 questionnaires (50% from internal departments, 36% from surgical departments and 14% from outpatient clinics) were analysed. The majority of the staff members (65%) knew that diabetes is diagnosed by glucose levels in blood. Of the 35% that did not know, 91% were nurses. The majority (75%) knew that diabetes is diagnosed during fasting conditions; however, most of the staff indicated that 12 h is needed. Only 25% knew of the designated test tube, and most of the staff indicated that a regular chemistry tube was the tube of choice for them. The staff exhibited poor level of knowledge regarding the parameters that influence the quality of the test. CONCLUSIONS: Staff members are not aware of the various aspects of diabetes diagnosis and the designated test tube for glucose measurements, and most of them use a tube that gives inaccurate measurements, therefore there is an urgent need to improve diabetes knowledge among staff members.

Parental sleep quality and continuous glucose monitoring system use in children with type 1 diabetes.

To compare sleep quality and sleep-wake patterns in parents of children with type 1 diabetes before routine use of the continuous glucose monitoring system (CGMS) and while using it. Thirteen parents completed the Pittsburg Sleep Quality Index (PSQI), a 7-day sleep diary, and wore an actigraph (a wristwatch-size motion detector) during the night for 1 week before pediatric use of CGMS and 4-8 weeks after initiating routine use of the CGMS. Mean age of parents (ten mothers, three fathers) was 39 (range 32-47) years; mean age of children was 9.3 years (range 5.5-16.5 years); mean disease duration was 3.4 (range 0.6-11.2) years. PSQI total score demonstrated similar quality of sleep with and without use of the CGMS (4.6 and 4.9, respectively, p = 0.45). Six of the 13 parents reported severe sleep problems (PSQI ≥ 5) with and without the CGMS. The sleep diary indicated a greater number of awakening episodes during CGMS use than without the CGMS (1.6 and 1, respectively, p = 0.03), and actigraphy documented an increase in the number of wake bouts (22.9 and 19.7, p = 0.03) as well as in total wake time (48.3 and 42.2 min, p = 0.03) during CGMS use as compared with the period prior to CGMS use. Although self-perception of sleep quality remained unchanged, CGMS use appeared to affect actual parental sleep continuity somewhat negatively. This should be made clear to parents who may hold expectations of improvement in sleep quality following initiation of CGMS use.

Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes.

AIMS: To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug-naÏve patients with type 2 diabetes. METHODS: After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized in a double-blind manner to initial treatment with a FDC of sitagliptin/metformin 50/500 mg twice daily (N = 261) or pioglitazone 30 mg per day (N = 256). Sitagliptin/metformin and pioglitazone were up-titrated over 4 weeks to doses of 50/1000 mg twice daily and 45 mg per day, respectively. Both treatments were then continued for an additional 28 weeks. RESULTS: From a mean baseline HbA1c of 8.9% in both groups, least squares (LS) mean changes in HbA1c at week 32 were -1.9 and -1.4% for sitagliptin/metformin and pioglitazone, respectively (between-group difference = -0.5%; p < 0.001). A greater proportion of patients had an HbA1c of <7% at week 32 with sitagliptin/metformin vs. pioglitazone (57% vs. 43%, p < 0.001). Compared with pioglitazone, sitagliptin/metformin treatment resulted in greater LS mean reductions in fasting plasma glucose (FPG) [-56.0 mg/dl (-3.11 mmol/l) vs. -44.0 mg/dl (-2.45 mmol/l), p < 0.001] and in 2-h post-meal glucose [-102.2 mg/dl (-5.68 mmol/l) vs. -82.0 mg/dl (-4.56 mmol/l), p < 0.001] at week 32. A substantially greater reduction in FPG [-40.5 mg/dl (-2.25 mmol/l) vs. -13.0 mg/dl (-0.72 mmol/l), p < 0.001] was observed at week 1 with sitagliptin/metformin vs. pioglitazone. A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of ß-cell function (HOMA-ß) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin. Both sitagliptin/metformin and pioglitazone were generally well tolerated. Sitagliptin/metformin led to weight loss (-1.4 kg), while pioglitazone led to weight gain (3.0 kg) (p < 0.001 for the between-group difference). Higher incidences of diarrhoea (15.3% vs. 4.3%, p < 0.001), nausea (4.6% vs. 1.2%, p = 0.02) and vomiting (1.9% vs. 0.0%, p = 0.026), and a lower incidence of oedema (1.1% vs. 7.0%, p < 0.001), were observed with sitagliptin/metformin vs. pioglitazone. The between-group difference in the incidence of hypoglycaemia did not reach statistical significance (8.4 and 4.3% with sitagliptin/metformin and pioglitazone, respectively; p = 0.055). CONCLUSION: Compared with pioglitazone, initial therapy with a FDC of sitagliptin and metformin led to significantly greater improvement in glycaemic control as well as a higher incidence of prespecified gastrointestinal adverse events, a lower incidence of oedema and weight loss vs. weight gain.

Jewish New Year associated with decreased point of care glucose in hospitalised patient population.

BACKGROUND: In individuals with diabetes, glycaemic control has been shown to be disrupted during the winter holiday period. OBJECTIVES: The aim of this study was to examine whether blood glucose levels are influenced by the Jewish New Year period in hospitalised individuals with diabetes. METHODS: At E. Wolfson Medical Center, Holon, Israel, blood glucose values from individuals hospitalised in internal medicine units were collected and analysed during the period surrounding Rosh Hashanah, the Jewish New Year, 2010. Values obtained from 4 to 7 September 2010 were categorised as preholiday values; values from 8 to 11 September 2010 were classed as holiday values; and values from 12 to 15 September 2010 were labelled postholiday values. All values were collected at point of care (POC) using an automated, institutional glucometer located in each department, the data from which is downloaded to a central database. RESULTS: A total of 3403 POC glucose values were recorded during the observation period. POC glucose values were significantly lower during the Rosh Hashanah holiday than the pre holiday or postholiday periods: 176.8 ± 81.3 mg/dl vs. 181.4 ± 78.8 mg/dl or 184.9 ± 83.02 mg/dl, p = 0.03. During the Rosh Hashanah holiday, mean patient age was significantly older than the preholiday or postholiday period: 77.4 ± 10.9 years vs. 74.9 ± 12.0 years or 75.3 ± 11.8 years, p < 0.0001; however, age predicted less than 1% of the variability in POC glucose: r = 0.02, p = 0.23. Significantly more women were hospitalised during the preholiday than during the holiday or postholiday periods. In a linear regression model, holiday period remained a significant independent predictor of POC glucose even after controlling for age and gender. CONCLUSIONS: Point of care glucose was significantly lower during the Rosh Hashanah period relative to preholiday and postholiday values. This may reflect a shift in the composition of the hospitalised patient population during the holidays towards older individuals with more restricted dietary intake.

Improved glycaemic control with reduced hypoglycaemic episodes and without weight gain using long-term modern premixed insulins in type 2 diabetes.

OBJECTIVE: The primary goal of the study was to evaluate retrospectively efficacy of long-term modern premixed insulin (MPI) administration. The secondary aims were to monitor weight gain, hypoglycaemia and compliance during MPI therapy. RESEARCH DESIGN AND METHODS: One hundred and fifteen outpatients with type 2 diabetes (64 male patients, 51 female patients; mean age 62.4±12.2 years; mean duration of diabetes 10±8 years; mean weight 84.3±14.8 kg) were included in this study. Patients were prescribed one of three MPIs thrice-daily: biphasic insulin lispro 25, biphasic insulin lispro 50, or biphasic insulin aspart 30. Metformin was combined with MPI in 81 patients. Data prior to and during MPI treatment were retrieved from computerised patient medical files. RESULTS: After a mean treatment period of 2.9±0.9 years, mean A1C levels and fasting blood glucose decreased from 8.7±1.4% and 193±59 mg/dl to 7.3±1.1% and 141±41 mg/dl (p<0.001 for both), respectively. Thirty-six per cent of the cohort achieved target A1C level of ≤7%. Serum triglycerides decreased from 183±109 mg/dl to 151±76 mg/dl (p<0.001). Weight did not change during MPI treatment. Frequency of minor hypoglycaemic episodes decreased significantly during MPI administration. No major hypoglycaemic event was reported. Number of incompliant patients decreased significantly from 39 to 25 (p=0.001) during MPI treatment. CONCLUSIONS: Modern premixed insulins represent an effective and safe long-term therapy for patients with type 2 diabetes. Specifically, the regimen of thrice-daily injections combined with metformin is a viable treatment option.

The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors.

OBJECTIVES: Sildenafil citrate is widely used for erectile dysfunction. The present study examined the short-term effects of sildenafil administration in individuals with cerebrovascular risk factors, including patients with a history of stroke. MATERIALS AND METHODS: Twenty-five consecutive male patients with erectile dysfunction and vascular risk factors were included in the study. A perfusion brain SPECT study was performed at baseline and 1 h after the oral administration of sildenafil. RESULTS: Associations between any of the risk factors and the perfusion scores were not detected, with the exception of stroke. Stroke patients showed significantly more areas with diminished perfusion after sildenafil administration compared to baseline. CONCLUSIONS: In patients with diabetes or hypertension, a dose of 50 mg sildenafil does not appear to produce detrimental effects on cerebral blood flow. However, patients with a history of stroke may be at increased risk of hemodynamic impairment after the use of sildenafil.

The effect of anti-inflammatory (aspirin and/or statin) therapy on body weight in Type 2 diabetic individuals: EAT, a retrospective study.

AIMS: Obesity is associated with inflammation. Anti-inflammatory interventions such as aspirin and statins (anti-IFRx) might be a novel approach to the treatment of obesity and Type 2 diabetes mellitus (T2DM). The present study was designed to determine whether exposure to anti-IFRx is associated with weight loss in T2DM patients. METHODS: Exposure to anti-IFRx was compared between T2DM patients with a history of weight loss (n = 100) and those with no weight loss or with weight gain (n = 102) during a 1-year follow-up period. Logistic regression was used to develop odds ratios for weight loss status. RESULTS: Subjects who lost weight were more frequently exposed to anti-IFRx (85.0 vs. 71.5%, P = 0.018) than subjects who maintained or gained weight during follow-up. The 158 subjects exposed to anti-IFRx were older (64.2 +/- 9.4 vs. 60.6 +/- 11.2 years, P = 0.04), had longer duration T2DM (14.5 +/- 9.5 vs. 9.0 +/- 9.4 years, P = 0.001), had greater prevalence of dyslipidaemia (72 vs. 19%, P < 0.0001) hypertension (57.3 vs. 38.1%, P = 0.03) and cardiovascular disease (37.7 vs. 9.5%, P < 0.0001) than subjects not exposed to anti-IFRx. In a logistic regression model for weight change status, anti-IFRx exposure was significantly associated with weight status (odds ratio = 2.3, 95% confidence interval 1.1-4.8, P = 0.02, an association that persisted), even after controlling for age, sex, baseline body mass index, years since diagnosis, OHA therapy and co-morbidities. CONCLUSIONS: Exposure to anti-IFRx more than doubled the odds of weight loss in T2DM patients. Results of this study justify a randomized clinical trial to determine definitively the role of anti-IFRx in weight loss in subjects with T2DM.

Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patients.

AIMS: To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin. METHODS: Forty obese Type 2 diabetic subjects (using insulin) were randomized to treatment with continuous subcutaneous infusion pump (CSII) (Minimed) or multiple daily insulin injections (MDI). At the end of the first 18-week treatment period, patients underwent a 12-week washout period during which they were treated with MDI plus metformin. They were then crossed-over to the other treatment for an 18-week follow-up period. Patients performed 4-point daily self blood-glucose monitoring (SBGM) on a regular basis and 7-point monitoring prior to visits 2, 8, 10 and 16. A subset of patients underwent continuous glucose monitoring using the Minimed(R) continuous glucose monitoring system (CGMS) at visits 2, 8, 10 and 16. A standard meal test was performed in which serum glucose was tested at fasting and once each hour for 6 h following a test meal. Glucose levels were plotted against time and the area under the curve (AUC) was calculated. HbA(1c), weight, daily insulin dose and hypoglycaemic episodes were recorded. RESULTS: In obese Type 2 diabetic patients already treated with insulin, treatment with CSII significantly reduced HbA(1c) levels compared with treatment with MDI. An additional CSII treatment benefit was demonstrated by reduced meal-test glucose AUC. Initial reduction of daily insulin requirement observed in CSII-treated subjects during the first treatment period was attributable to a period effect and did not persist over time. CONCLUSIONS: In the intent-to-treat analysis, CSII appeared to be superior to MDI in reducing HbA(1c) and glucose AUC values without significant change in weight or insulin dose in obese, uncontrolled, insulin-treated Type 2 diabetic subjects.

Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach.

BACKGROUND: Benzodiazepines are the most frequently used drug for the treatment of insomnia. Prolonged use of benzodiazepine therapy is not recommended. However, many patients, particularly older patients, have difficulties discontinuing therapy. Melatonin, a hormone that is produced at night by the pineal gland, promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy. OBJECTIVE: To assess whether the administration of melatonin could facilitate the discontinuation of benzodiazepine therapy in patients with insomnia. METHODS: Thirty-four subjects receiving benzodiazepine therapy were enrolled in the 2-period study. In period 1, patients received (double-blinded) melatonin (2 mg in a controlled-release formulation) or a placebo nightly for 6 weeks. They were encouraged to reduce their benzodiazepine dosage 50% during week 2, 75% during weeks 3 and 4, and to discontinue benzodiazepine therapy completely during weeks 5 and 6. In period 2, melatonin was administered (single-blinded) for 6 weeks to all subjects and attempts to discontinue benzodiazepine therapy were resumed. Benzodiazepine consumption and subjective sleep-quality scores were reported daily by all patients. All subjects were then allowed to continue melatonin therapy and follow-up reassessments were performed 6 months later. RESULTS: By the end of period 1, 14 of 18 subjects who had received melatonin therapy, but only 4 of 16 in the placebo group, discontinued benzodiazepine therapy (P = .006). Sleep-quality scores were significantly higher in the melatonin therapy group (P = .04). Six additional subjects in the placebo group discontinued benzodiazepine therapy when given melatonin in period 2. The 6-month follow-up assessments revealed that of the 24 patients who discontinued benzodiazepine and received melatonin therapy, 19 maintained good sleep quality. CONCLUSION: Controlled-release melatonin may effectively facilitate discontinuation of benzodiazepine therapy while maintaining good sleep quality.

[Efficacy and safety of acarbose treatment of NIDDM].

An uncontrolled multicenter study of the efficacy and safety of treatment of diabetes with acarbose was conducted on 169 NIDDM patients in 12 medical centers in Israel. Acarbose was administered for 19 weeks, and the patients were followed for an additional 12 weeks. A substantial decrease in HbA1c levels from 8.5% to 7.5% (p < 0.001) and in postprandial serum glucose levels from 283.6 mg/dl to 248.5 mg/dl (p < 0.01) was seen during treatment. On follow-up, HbA1c levels increased by 0.45% and postprandial serum glucose rebounded from 256.4 mg/dl to 287.9 mg/dl. Acarbose was shown to be effective in treating NIDDM and to be safe and well-tolerated.