Intermittent Intensive Insulin Therapy for Type 2 Diabetes: Effects on Hypoglycemia,Weight Gain,and Quality of Life Over 2 Years

Objective: In early type 2 diabetes (T2DM), the administration of short-term intensive insulin therapy (IIT) can induce glycemic remission for a year thereafter, but this effect ultimately wanes. In this context, intermittently repeating short-term IIT could provide a strategy for maintaining the otherwise transient benefits of this intervention. However, the viability of this strategy would be contingent upon not inducing undesirable effects of insulin therapy such as excessive hypoglycemia and fat deposition. We thus sought to evaluate the effect of administering short-term IIT every 3 months on hypoglycemia, weight gain, and quality of life in early T2DM.Methods: In this 2-year pilot trial, 24 adults with T2DM of 2.0 ± 1.7 years duration and hemoglobin A1c of 6.4 (46 mmol/mol) ± 0.1% were randomized to 3 weeks of IIT (glargine, lispro) followed by either (1), repeat IIT for up to 2 weeks every 3 months or (2), daily metformin. IIT was titrated to target near-normoglycemia (premeal glucose 4 to 6 mmol/L; 2-hour postmeal <8 mmol/L). Participants were assessed every 3 months, with quality of life (QOL) evaluated annually.Results: The rate of hypoglycemia (<3.5 mmol/L) was low in the metformin and intermittent IIT arms (0.37 versus 0.95 events per patient-year; P = .28). There were no differences between the groups in changes over time in overall, central, or hepatic fat deposition (as reflected by weight &lsqb;P = .10], waist-to-hip ratio &lsqb;P = .58], and alanine aminotransferase &lsqb;P = .64], respectively). Moreover, there were no differences between the groups in QOL at 1- and 2-years.Conclusion: Intermittent short-term IIT may be safely administered in early T2DM without excessive adverse impact on hypoglycemic risk, anthropometry, or QOL.Abbreviations: ALT = alanine aminotransferase; HbA1c = hemoglobin A1c; IIT = intensive insulin therapy; ISSI-2 = insulin secretion-sensitivity index-2; OGTT = oral glucose tolerance test; QOL = quality of life; SF-36 = medical outcomes study 36-item short-form health survey; T2DM = type 2 diabetes     

Analysis of Factors That Determine Weight Gain during Smoking Cessation Therapy

Cigarette smokers are generally known to gain weight after quitting smoking, and such weight gain is thought to contribute to the worsening of glucose tolerance. While smoking cessation therapy such as nicotine replacement is useful to minimize post-cessation weight gain, substantial gain occurs even during the therapy. The purpose of the present study was to identify factors associated with weight gain during smoking cessation therapy. We evaluated 186 patients(132 males and 54 females)who visited our outpatient clinic for smoking cessation, and successfully achieved smoking abstinence. We performed gender-adjusted regression analysis for the rate of BMI increase from the beginning of cessation to 3 months after initiation. Furthermore, we performed multivariate analysis to investigate factors that determine the BMI increase after smoking cessation. The mean BMI significantly (p<0.0001) increased from 23.5±3.6 kg/m² at the initial consultation to 23.9±3.8 kg/m² at 3 months after the start of therapy. There was no significant difference in the extent of BMI increase between nicotine patch and varenicline therapy groups. Factors significantly correlated with the %BMI increase at 3 months after the start of therapy were triglyceride (p = 0.0006, βa = 0.260), high-density lipoprotein cholesterol (p = 0.0386, βa = −0.168), daily cigarette consumption (p = 0.0385, βa = 0.154), and the Fagerström Test for Nicotine Dependence (FTND) score (p = 0.0060, βa = 0.203). Stepwise multivariate analysis demonstrated that triglyceride and the FTND score were the factors determining the post-cessation BMI increase and that the FTND score was the strongest one. The present study demonstrated that smokers with a high FTND score are more likely to gain weight during smoking cessation therapy. Thus, smokers with a high nicotine dependency may require intervention against weight gain in the cessation clinic.     

Consumption of Clarified Grapefruit Juice Ameliorates High-Fat Diet Induced Insulin Resistance and Weight Gain in Mice

To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25–50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ), ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13–17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet.     

Changes in Skeletal Muscle Vascular Resistance with Weight Gain: Associations with Insulin and Sympathetic Activity

BORNE, AGATHA T., ALYCIA A. TRUETT, MICHELLE P. MONTEIRO, JULIA VOLAUFOVA, AND DAVID B. WEST. Changes in skeletal muscle vascular resistance with weight gain: associations with insulin and sympathetic activity. Obes Res. 1999;7:68–75. Objective : This study was designed to characterize changes in peripheral vascular resistance with weight gain, and whether these changes are correlated with insulin and/or sympathetic activity. Research Methods and Procedures : Femoral vascular resistance (FVR), mean arterial pressure, heart rate, and plasma insulin were measured before and during overfeeding in seven dogs with unilateral lumbar ganglionectomy (L₃ to L₆). Measurements were taken standing and while walking on a treadmill. Results : There was a significant main effect of weight gain to increase mean arterial pressure (16.5±8.4 mmHg and 12.5±6.8 mmHg increase for standing and walking baseline, respectively) and heart rate (increase from week 1 of 31.6±10.6 beats/minute standing and 38.3±9.1 walking beat/minute). FVR increased immediately with overfeeding/ weight gain [standing: denervated (DNX):1.32±0.3 to 2.34±0.5; intact: 0.88±0.17 to 1.9±0.33 mmHg/mL-min^?1], but returned to baseline with continued weight gain. Return of FVR to baseline occurred between weeks 2 and 3 of overfeeding in the DNX limb, but did not return to baseline until week 6 in the innervated limb. These changes were not correlated with plasma insulin levels. Discussion : These data suggest that vascular resistance may be normal in the obese, but increases in vascular resistance occur early with weight gain (before changes in arterial pressure). This initial increase in vascular resistance could initiate the series of events leading to obesity-associated hypertension. Additionally, changing vascular resistance during weight gain may be influenced by sympathetic activity, because DNX limb FVR returned to baseline ?3 weeks earlier than the innervated limb.     

Insulin Pump Therapy in Patients with Diabetes Undergoing Surgery

ObjectiveTo assess perioperative management of patients with diabetes mellitus who were being treated with insulin pump therapy.MethodsWe reviewed records for documentation of insulin pump status and glucose monitoring during preoperative, intraoperative, and postanesthesia care unit (PACU) phases of surgery.ResultsThirty-five patients (21 men) with insulin pumps underwent surgical procedures between January 1, 2006, and December 31, 2010. Mean age was 56 years, mean diabetes duration was 31 years, and mean duration of insulin pump therapy was 7 years. All patients were white, and 29 had type 1 diabetes mellitus. Of the 50 surgical procedures performed during the study period, 16 were orthopedic, 9 were general surgical, 7 were urologic, and 7 were kidney transplant operations; the remaining 11 procedures were in other surgical specialties. The mean (± standard deviation) time in the preoperative area was 118 ± 75 minutes, mean intraoperative time was 177 ± 102 minutes, and mean PACU time was 170 ± 78 minutes. Of the 50 procedures, status of pump use was documented in 32 cases in the preoperative area, 14 cases intraoperatively, and 30 cases in the PACU. Glucose values were recorded in 47 cases preoperatively, 30 cases intraoperatively, and 48 cases in the PACU.ConclusionsResults showed inconsistent documentation of pump use and glucose monitoring throughout the perioperative period, even for patients with prolonged anesthesia and recovery times. It was often unclear whether the pump was in place and operational during the intraoperative period. Guidelines should be developed for management of insulin pump–treated patients who are to undergo surgery. (Endocr Pract. 2012;18:49-55)     

Diabetes Mellitus: Distinguishing Between Patients Receiving Insulin and Those Requiring Insulin Therapy

Fifteen patients with maturity onset type diabetes, all of whom had received insulin for periods of one to thirty-five years, were admitted to hospital and insulin treatment was discontinued. Within 24 to 48 hours each patient was given an intravenous tolbutamide test, following which all were given either diet therapy alone or diet therapy plus oral agents. If significant hyperglycemia or ketonemia resulted, insulin therapy was reinstituted.Approximately 50 percent (8 of 15) of the patients showed improvement in fasting blood sugar levels following discontinuation of insulin. It was not possible to distinguish the insulin independent from the insulin dependent group using such criteria as age, sex, degree of overweight, insulin dosage, duration of diabetes or duration of insulin therapy. However, using the intravenous tolbutamide test it was possible to differentiate between the two groups. Those who did not require insulin responded to intravenous tolbutamide with a glucose decrease greater than 10 percent from the initial value. The insulin dependent group had either no glucose decrease or a rise in blood glucose following intravenous administration of tolbutamide.     

Maternal Insulin Sensitivity During Pregnancy Predicts Infant Weight Gain and Adiposity at 1 Year of Age

Emerging evidence suggests that fetal environmental exposures impact on future development of obesity. The objectives of this study were to assess the relationships between (i) maternal insulin sensitivity and glucose tolerance status in pregnancy and (ii) early infant weight gain and adiposity in the first year of life. In this prospective cohort study, 301 women underwent oral glucose tolerance testing for assessment of glucose tolerance status and insulin sensitivity (IS_OGTT) in pregnancy. Their infants underwent anthropometric assessment at 12 months of age, including determination of weight gain in the first year of life and sum of skinfold thickness (SFT), a measure of infant adiposity. Infant weight gain and sum of SFT at 12 months did not differ according to maternal glucose tolerance status. On univariate analyses, weight gain from 0 to 12 months and sum of SFT were negatively associated with maternal IS_OGTT during pregnancy. On multiple linear regression analysis, negative independent predictors of weight gain from 0 to 12 months were maternal IS_OGTT during pregnancy (t = ?2.73; P = 0.007), infant female gender (t = ?3.16; P = 0.002), and parental education (t = ?1.98; P = 0.05), whereas white ethnicity was a positive independent predictor (t = 2.68; P = 0.008). Maternal IS_OGTT (t = ?2.7; P = 0.008) and parental education (t = ?2.58; P = 0.01) were independent negative predictors of sum of SFT at 12 months. Independent of maternal glucose tolerance status, maternal insulin resistance during pregnancy is associated with increased infant weight gain and adiposity over the first year of life. Further longitudinal study to evaluate obesity in this group of children will increase our understanding of the contribution of the intrauterine environment to their long‐term health.     

Effect of Serum Leptin on Weight Gain Induced by Olanzapine in Female Patients with Schizophrenia

Background

Olanzapine (OLZ) treatment is associated with a high risk of weight gain, and may cause abnormalities in glycolipid metabolism. Therefore, the underlying mechanism of OLZ-related weight gain is needed to clarify but not yet been adequately determined. In recent years, adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α, which play important roles in energy homeostasis, have been suggested as biomarkers of weight gain. Here, we determined if baseline plasma concentrations of leptin, adiponectin, and TNF-α predict weight gain following OLZ treatment.

Methods

We recruited 31 schizophrenia outpatients (12 men and 19 women, 28.8 ± 10.2 years old) that were unmedicated or on another antipsychotic monotherapy medication. Baseline body mass index (BMI) and plasma levels of leptin, adiponectin, and TNF-α were obtained. All patients started or were switched to OLZ monotherapy for a maximum of 1 year. BMI was also obtained at the endpoint.

Results

Mean BMI change following OLZ treatment was 2.1 ± 2.7 kg/m². BMI change from baseline to endpoint negatively-correlated with baseline leptin levels in female patients (r = −0.514, P = 0.024), but not male patients. Baseline adiponectin or TNF-α levels were not correlated with BMI change.

Conclusion

Baseline plasma leptin can have an effect on subsequent weight gain following OLZ treatment in female patients with schizophrenia.     

Attitudes Toward Weight Gain in Pregnancy

Recently, there has been increased interest in the influence of maternal prenatal nutrition on the course and outcome of pregnancy. Evidence has accumulated that a woman''s weight before pregnancy and the weight gained during pregnancy directly affect infant birth weight, incidence of neonatal mortality, and growth and development of the infant during the first year of life. Although recent recommendations for weight gain in pregnancy have been liberalized, a survey of 195 pregnant women who had prenatal visits in both clinic and private offices showed deficiencies in their understanding of the subject. Some 37 percent of women believed they should gain 20 pounds (9 kg) or less during pregnancy. Eight percent admitted to dieting before at least one antenatal visit and 54 percent thought their doctor would not be concerned about too little weight gained during pregnancy. This suggests that many women and some doctors are still ignorant of current concepts of proper nutrition during pregnancy. Apparently, increased lay and professional educational efforts are needed.     

Analysis of Effectiveness of Human U-500 Insulin in Patients Unresponsive to Conventional Insulin Therapy

ObjectiveTo present a retrospective analysis of the effects of human U-500 insulin in 20 patients with type 2 diabetes and insulin resistance.MethodsMedical records of 20 patients with type 2 diabetes who had received U-500 insulin for at least 6 months were reviewed to determine glycemic control before and after this therapy. Human regular U-500 insulin therapy was initiated at a unit dosage equivalent to the previous standard insulin dosage. Comparisons of hemoglobin A1c levels, insulin doses, and body mass index at baseline and 6 months after changing to U-500 insulin therapy were analyzed.ResultsIn the 10 female and 10 male study subjects, the mean (± SD) hemoglobin A1c level was 9.59 ± 1.37% initially, and it decreased to 8.53 ± 1.11% at 3 months and to 7.83 ± 1.26% at 6 months after initiation of U-500 insulin therapy. In comparison with baseline, these decreases were statistically significant. The amount of insulin used and the body mass index did not change significantly from baseline to 6 months after initiation of U-500 insulin treatment.ConclusionAnalysis of data suggests that U-500 insulin therapy yields improved glycemic control in insulin-resistant patients who have poor control of blood glucose with use of standard insulin regimens. There is no proof, however, that improved glycemic control by this method decreases diabetes-related complications or improves survival. Further studies must be performed before U-500 insulin can be recommended as a standard therapy for patients with insulin resistance. (Endocr Pract. 2005;11:305-307)     

Prevention of Weight Gain in Adult Patients With Type 2 Diabetes Treated With Pioglitazone

Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain. Our study was designed to examine the effectiveness of three lifestyle‐treatment programs of varying intensity on prevention of pioglitazone‐induced weight gain and to measure the composition of the change in body weight. Thirty‐nine adult overweight and obese subjects with type 2 diabetes mellitus were all treated with pioglitazone and prospectively randomized to one of three lifestyle‐treatment programs with increasing level of intensity for 24 weeks. Body composition was measured by dual‐energy X‐ray absorptiometry (DXA), computed tomography, and multifrequency bioimpedance analysis both before and after therapy. Subjects demonstrated a “dose‐response” effectiveness to three levels of lifestyle intervention to mitigate pioglitazone‐induced weight gain. Mean (s.d.) weight change (kg) for the usual, standard, and intensive lifestyle groups were 4.9 ± 4.9 (P = 0.005), 1.8 ± 3.4 (P = 0.02), and ?0.2 ± 4.4 (NS) respectively. Total body fat increased 2.6 ± 3.4 kg (P = 0.04) for the usual group and decreased for the intensive group ?0.4 ± 3.5 (NS). Change in abdominal subcutaneous and visceral adipose tissue (VAT) did not differ between groups, although ratio of visceral/subcutaneous fat decreased for the standard and intensive groups (NS). Both usual (P < 0.05) and standard care (NS) groups gained total body water. This is the first prospective, randomized study that demonstrates the beneficial effect of participation in a comprehensive lifestyle‐weight‐management program on lessening of weight gain associated with pioglitazone.