Elevated Fasting Glucose Levels Research Articles

Effect of telmisartan on cardiovascular complications associated with streptozotocin diabetic rats

Angiotensin receptor blockers provide cardiovascular protection in heart failure patients. We have studied the effect of 8 weeks treatment with telmisartan (5 mg kg(-1) day(-1)) on cardiovascular complications associated with streptozotocin (STZ) diabetic rats. Wistar rats were made diabetic with STZ (45 mg kg(-1), iv). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, reduction in heart rate and cardiac hypertrophy. Chronic treatment with telmisartan significantly (P < 0.05) prevented STZ induced hypertension and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly (P < 0.05) reduced the elevated cholesterol, very low density lipoprotein (VLDL) and triglyceride levels in diabetic rats and increased the lower high density lipoprotein (HDL)-cholesterol levels. Further, telmisartan produced a significant (P < 0.05) reduction in the elevated creatinine levels, CRP and levels of other cardiac enzyme markers like Lactate de-hydrogenase and creatinine kinase of diabetic rats. STZ-induced bradycardia was also prevented by telmisartan treatment and it also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac hypertrophy index and left ventricular hypertrophy index of diabetic rats. Our data suggest that telmisartan prevents not only the STZ-induced metabolic abnormalities, but also cardiovascular complications.

Metabolic Syndrome Is Associated With Silent Ischemic Brain Lesions

Metabolic syndrome (MetS) is a recognized risk factor for stroke, but it is unclear whether MetS is also related to subclinical ischemic lesions. We examined the association of MetS with the prevalence of silent brain infarction, periventricular hyperintensity, and subcortical white matter lesions in healthy adults. We conducted a cross-sectional study in 1151 Japanese healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS was diagnosed using the criteria by the National Cholesterol Education Adult Treatment Panel III. After adjusting for age and other factors, MetS was significantly associated with silent brain infarction, periventricular hyperintensity and subcortical white matter lesions. Among the MetS components, elevated blood pressure was commonly associated with all types of lesions. Dyslipidemia and elevated fasting glucose levels were associated with subcortical white matter lesions and periventricular hyperintensities, respectively. Positive trends were observed between the number of MetS components and prevalence of silent lesions. MetS is associated with the prevalence of silent lesions independent of other risk factors. The clustering of MetS components tends to increase the prevalence of silent lesions.

Low level of Lemon Balm (Melissa officinalis) essential oils showed hypoglycemic effects by altering the expression of glucose metabolism genes in db/db mice

The effects of the lemon balm essential oils (LBEO) in the db/db mice were examined. Mice were divided into four groups and the LBEO was orally administered for 6 weeks: saline, control; 0.15mg/d, LBEO1; 0.05mg/d, LBEO2; 0.0125mg/d, LBEO3. The LBEO showed biphasic effects on plasma glucose levels; the low level feeding was hypoglycemic but the medium and the high levels exerted hyperglycemic effects. The LBEO3 group showed reduced fasting glucose (65%, P&lt;0.05) and triglyceride concentrations compared with the controls. Glucose tolerance, assessed by oral glucose tolerance test, was improved in this group accordingly. However, in the LBEO1 and the LBEO2 groups, glucose tolerance was worsened according to the elevated fasting glucose levels compared with the controls (33% and 27% elevation in the LBEO1 and the LBEO2, respectively P&lt;0.05). Plasma GOT and GPT levels were elevated in these groups as well. The hypoglycemic mechanism of low level feeding of the LBEO was further investigated with quantifying the expression of the glucose metabolism genes by real time PCR. The glucokinase and the GLUT 4 gene expressions were significantly upregulated, however, the expression of glucose‐6‐phosphase and phosphoenolpyruvate carboxykinase were downregulated in the mouse livers of the LBEO3 group. The results suggest that the LBEO may be hypoglycemic when administered at low concentration. These effects may be due to the enhanced glucose uptake and the inhibition of gluconeogenesis in the livers.

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2) Which endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses? Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined. GIP and GLP-1 levels increased significantly in both experiments (P < 0.0001). In patients with type 2 diabetes, the initial GIP response was exaggerated compared with control subjects after mixed meal (P < 0.001) but not after oral glucose ingestion (P = 0.98). GLP-1 levels were similar in all three groups in both experiments. GIP responses were 186 +/- 17% higher after mixed meal ingestion than after the oral glucose load (P < 0.0001), whereas GLP-1 levels were similar in both experiments. There was a strong negative association between fasting glucagon and integrated FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and integrated glucagon levels after glucose or meal ingestion and female sex were positively related to GLP-1 concentrations. Incretin levels were unrelated to measures of glucose control or insulin secretion. Deteriorations in glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1 levels. This suggests that the defects in GLP-1 concentrations previously described in patients with long-standing type 2 diabetes are likely secondary to other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP-1 concentrations appear to be regulated by different factors and are independent of each other.

Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women

An unresolved issue in the field of diet and health is if and how changes in meal frequency affect energy metabolism in humans. We therefore evaluated the influence of reduced meal frequency without a reduction in energy intake on glucose metabolism in normal-weight, healthy male and female subjects. The study was a randomized crossover design, with two 8-week treatment periods (with an intervening 11-week off-diet period) in which subjects consumed all of their calories for weight maintenance distributed in either 3 meals or 1 meal per day (consumed between 4:00 pm and 8:00 pm). Energy metabolism was evaluated at designated time points throughout the study by performing morning oral glucose tolerance tests and measuring levels of glucose, insulin, glucagon, leptin, ghrelin, adiponectin, resistin, and brain-derived neurotrophic factor (BDNF). Subjects consuming 1 meal per day exhibited higher morning fasting plasma glucose levels, greater and more sustained elevations of plasma glucose concentrations, and a delayed insulin response in the oral glucose tolerance test compared with subjects consuming 3 meals per day. Levels of ghrelin were elevated in response to the 1-meal-per-day regimen. Fasting levels of insulin, leptin, ghrelin, adiponectin, resistin, and BDNF were not significantly affected by meal frequency. Subjects consuming a single large daily meal exhibit elevated fasting glucose levels and impaired morning glucose tolerance associated with a delayed insulin response during a 2-month diet period compared with those consuming 3 meals per day. The impaired glucose tolerance was reversible and was not associated with alterations in the levels of adipokines or BDNF.

Gender-related hormonal risk factors for oral cancer

Oral cancer (OC) is a neoplasm with fairly high male to female ratio in most populations. The conspicuously lower incidence of this tumor among women than man is suggestive of certain endocrine involvement in its development. The aim of the present case-control study was to clarify the origin of this gender-specific risk of OC incidence. 2660 inpatients (530 females and 2130 males) with squamous cell OC at the Department of Oral and Maxillofacial Surgery were included in a case-control study. Smoking, alcohol consumption, elevated fasting serum glucose level and menopausal histories of female cases were registered. Smoking and excessive alcohol intake proved to be strong risk factors for OC both in the male and female group. However, moderate alcohol consumption was a weaker risk factor for male patients, and it presented no risk for female cases. Elevated fasting glucose level was not a demonstrable OC risk factor among males, however, it proved to be strong risk factor for OC among female patients, especially in gingival cancer cases. The almost exclusively postmenopausal state of female OC patients and the long mean interval (17 years) between their menopause and OC diagnosis suggested an important role of estrogen deficiency in OC epidemiology. The significantly younger mean age at menopause and the significantly higher rate of hysterectomy among female OC cases in comparison with their controls also support the estrogen deficiency hypothesis. This novel hypothesis of estrogen deficiency and elevated fasting glucose as risk factors for OC in postmenopausal women may provide new insights into the etiology of oral malignancies.

Physical Activity's Impact on the Relationship Between Socioeconomic Status & the Metabolic Syndrome

PURPOSE: To examine the associations between socioeconomic status (SES), leisure-time physical activity (LTPA) and the metabolic syndrome in 6,904 men (M = 42, SEM = 0.45 years old) and 7,883 women (M = 44, SEM = 0.52 years old) enrolled in NHANES III. METHODS: SES was expressed as educational attainment (< high school, high school, college, or > college), income level (< $10,000; $10,000–19,000, $20,000–34,999; $35,000-$49,000; >$50,000), and the poverty index ratio (living in poverty or not in poverty). LTPA was classified as active (reported ≥ 1 day/week of moderate- and/or vigorous-intensity activity) and inactive (no LTPA). The metabolic syndrome was denned as the presence of the three or more of the following factors: 1) central obesity; 2) elevated triglyceride concentrations; 3) low HDL-C concentrations; 4) elevated blood pressure; or 5) elevated fasting glucose levels. Logistic regression was used to examine the relationship between SES indicators and the metabolic syndrome, adjusting for age, race and sex, in the total sample and in subgroups denned by LPTA level. RESULTS: The odds for metabolic syndrome were elevated for each indicator of lower SES (educational attainment: OR = 1.28 to 1.54, p<05; income level: OR = 1.30 to 1.45, p<05; poverty index ratio: OR = 1.25, p<05). Among active adults, the odds of the having less education and living in poverty was higher for those with the metabolic syndrome compared to referent groups (educational attainment: OR = 1.37 to 1.62, p<05; poverty index ratio: OR = 1.50, p<05). Further, for the active adults there is a suggestion of increasing risk with decreasing educational attainment, although this trend is non-significant. Among inactive adults, no relationship existed between SES and the metabolic syndrome compared to referent groups (educational attainment: OR = 0.65 to 1.15, p>.05; income level: OR = 1.50 to 2.11, p>.05; poverty index ratio: OR = 1.21, p>.05). CONCLUSIONS: SES is inversely associated with the risk for the metabolic syndrome. Among active adults, low SES is associated with increased risk for the metabolic syndrome; however, among inactive adults, the risk for the metabolic syndrome is similar across different SES levels.

The relationship of heart rate and heart rate variability to non‐diabetic fasting glucose levels and the metabolic syndrome: The Cardiovascular Health Study

Increased heart rate (HR) and diminished heart rate variability (HRV) are signs of early cardiovascular autonomic neuropathy. We tested the hypotheses that increased HR and diminished HRV are present in people: (i) with increased fasting glucose (FG) levels not in the range of diabetes mellitus (DM), and (ii) in people with the metabolic syndrome (MetS) independent of elevated FG levels. HR and HRV were determined in 1267 adults (mean age 72 years) who had Holter monitoring and FG measures: 536 had normal FG levels (NORM, FG 4.5-5.5 mmol/l), 363 had mildly impaired FG (IFG-1, FG 5.6-6.0 mmol/l), 182 had significantly impaired FG (IFG-2, FG 6.1-6.9 mmol/l) and 178 had DM (FG > 6.9 mmol/l or use of glucose-lowering agents/insulin). HR and HRV in NORM/IFG-1 was further compared by the number of components of the MetS and compared by the presence or absence of MetS in IFG-2/DM. HRV indices were more impaired in IFG-2 and DM than in NORM or IFG-1. There were few differences in HRV indices between NORM and IFG-1 or between IFG-2 and DM. In NORM/IFG-1 participants, having > or = 2 components of the MetS was associated with a greater decrease in HRV compared with having no or one components. In IFG-2/DM participants, MetS was associated with decreased HRV compared with no MetS. Increased HR and diminished HRV occur in the non-diabetic FG range. Diminished HRV is associated with the MetS, independent of FG levels. Both these results suggest that factors associated with increasing non-diabetic FG levels and the MetS play a role in the onset of cardiac autonomic impairment.

Multiple Risk Factors for Cardiovascular Disease and Diabetes Mellitus

In the past 25 years, obesity and diabetes mellitus have overtaken cigarette smoking, dyslipidemia, and hypertension as risk factors for coronary heart disease. Data from a Centers for Disease Control and Prevention (CDC) survey of 50 states revealed that, in 2000, the prevalence of obesity among US adults was approximately 20%, a 61% increase from the 1991 prevalence rate. Currently, most adults (≥56%) are overweight, approximately 1 in 5 is obese, and 7.3% have diabetes. Overweight and obesity increase the risk for hospitalization and death from cardiovascular disease (CVD) and type 2 diabetes at all levels of risk and independently of other risk factors. In particular, abdominal obesity (assessed indirectly by measuring waist circumference) may be associated with clustering of cardiovascular and metabolic risk factors (i.e., hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol levels, high blood pressure, and elevated levels of fasting glucose) known as the metabolic syndrome. Patients with even minimal abnormalities in any 3 of the 5 risk factors for the metabolic syndrome are at heightened risk for CVD or diabetes. It is estimated that 47 million US adults, 25% of the population, have ≥3 metabolic syndrome components. Abdominal obesity is the most common, followed by low HDL cholesterol levels, high blood pressure, and high levels of triglycerides. The risk for disease increases over time as the number of metabolic syndrome characteristics accumulates; therefore, early intervention is warranted. Given the prevalence and potentially deadly consequences of the metabolic syndrome, it is imperative for physicians to recognize the presence of these risk factors in their patients and to familiarize themselves with the recommended treatment strategies.

Ten‐year incidence of diabetes in older Australians: the Blue Mountains Eye Study

To estimate the incidence of diabetes and impaired fasting glucose (IFG), and increased risk associated with the metabolic syndrome, in a representative population-based sample of older Australians. The Blue Mountains Eye Study examined 3654 residents aged 49 + years (82.4% response rate) during 1992-1994, and re-examined 2335 (75.1% of survivors) during 1997-1999 and 1952 (75.6% of survivors) during 2002-2004; 2123 participants with normal blood glucose levels at baseline were considered at risk of developing incident diabetes. Incident diabetes (or IFG) was defined in participants at risk who were newly diagnosed by a physician during the follow-up or found to have a fasting blood glucose level >or= 7.0 mmol/L (or 5.6-6.9 mmol/L). Kaplan-Meier cumulative 10-year incidence was calculated. The overall 10-year incidence of diabetes and IFG was 9.3% and 15.8%, respectively. Participants with metabolic syndrome at baseline had a higher risk of incident diabetes than those without metabolic syndrome (29.2% v 8.6%). Baseline factors associated with incident diabetes were elevated fasting glucose level (adjusted odds ratio [OR], 4.5; 95% CI, 3.4-6.1 per mmol/L), obesity (OR, 2.0; 95% CI, 1.3-2.8), diabetes family history (OR, 1.7; 95% CI, 1.2-2.5), current smoking (OR, 1.6; 95% CI, 1.0-2.7) and high density lipoprotein cholesterol level < 1.0 mmol/L (OR, 2.4; 95% CI, 1.5-3.8). Similar baseline factors were associated with incident IFG. This population-based study provides data on the incidence of diabetes and IFG in an older, predominantly white population, and confirms that metabolic and lifestyle factors are major risk factors for diabetes.

Prevalence of the metabolic syndrome in an incident dialysis population

The National Heart, Lung, and Blood Institute's National Cholesterol Education Program 2001 Adult Treatment Panel III report defined the metabolic syndrome as having at least 3 of the following 5 criteria: abdominal obesity, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, an elevated blood pressure, and an elevated fasting glucose. Evidence is accumulating to suggest that the metabolic syndrome predisposes to cardiovascular disease (CVD). End-stage kidney disease (ESKD) patients requiring dialysis have a substantially elevated risk of CVD morbidity and mortality. Dialysis patients' increased risk can be partially explained by traditional and nontraditional risk factors. The prevalence of the metabolic syndrome in dialysis patients is unknown. This retrospective, cross-sectional study of 202 incident dialysis patients examined the prevalence of the metabolic syndrome at the time of renal replacement therapy initiation. The study group was compared with all incident dialysis patients in 2002 on file with the U.S. Renal Data System. Females represented 39.1% of the study population. Blacks composed 34.7% of the study group. Diabetes was the etiology of ESKD in 44.6% of our patients. Surrogate criteria were used for the Adult Treatment Panel III risk factors of abdominal obesity and elevated fasting glucose levels. Overall, the prevalence of the metabolic syndrome was 69.3% in our population and was especially prevalent among diabetic, female, and white ESKD patients. Study limitations included the use of surrogate markers for 2 criteria of the metabolic syndrome and dependence on the Medical Evidence Report (Form 2728) for baseline characteristics. In summary, the metabolic syndrome is highly prevalent in incident dialysis patients.

Mist1-null mice are resistant to streptozotocin-induced β cell damage

Streptozotocin (STZ), a pancreatic β cell toxin, is used to induce diabetic conditions by targeting the Glut-2 transporter. We have recently identified decreased Glut-2 expression in β cells of mice lacking the transcription factor Mist1 ( Mist1 KO ). Given the loss in Glut-2 expression, we examined whether Mist1 KO β cells have an increased resistance to STZ. Mist1 KO and wild-type (WT) female mice received a single 100 or 200 mg/kg injection of STZ, and resting glucose levels and islet morphology were assayed 3–7 days after injection. Ten-month-old Mist1 KO mice have less β cell damage when exposed to high levels of STZ while 2-month-old Mist1 KO mice exhibit a dose-dependent resistance. Surprisingly, Mist1 KO mice still have elevated fasting glucose levels when compared to WT mice. These results suggest that while Mist1 KO islets have increased resistance to STZ, additional effects outside of β cell loss alter blood glucose homeostasis.

Fasting Glucose Levels and Incident Diabetes Mellitus in Older Nondiabetic Adults Randomized to Receive 3 Different Classes of Antihypertensive Treatment

Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension. The significance of this finding is uncertain. Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic, calcium-channel blocker, or angiotensin-converting enzyme inhibitor on fasting glucose (FG) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus (DM) in 3 treatment groups. We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) among nondiabetic participants who were randomized to receive treatment with chlorthalidone (n = 8419), amlodipine (n = 4958), or lisinopril (n = 5034) and observed for a mean of 4.9 years. Mean FG levels increased during follow-up in all treatment groups. At year 2, those randomized to the chlorthalidone group had the greatest increase (+8.5 mg/dL [0.47 mmol/L] vs +5.5 mg/dL [0.31 mmol/L] for amlodipine and +3.5 mg/dL [0.19 mmol/L] for lisinopril). The odds ratios for developing DM with lisinopril (0.55 [95% confidence interval, 0.43-0.70]) or amlodipine (0.73 [95% confidence interval, 0.58-0.91]) vs chlorthalidone at 2 years were significantly lower than 1.0 (P<.01). There was no significant association of FG level change at 2 years with subsequent coronary heart disease, stroke, cardiovascular disease, total mortality, or end-stage renal disease. There was no significant association of incident DM at 2 years with clinical outcomes, except for coronary heart disease (risk ratio, 1.64; P = .006), but the risk ratio was lower and nonsignificant in the chlorthalidone group (risk ratio, 1.46; P = .14). Fasting glucose levels increase in older adults with hypertension regardless of treatment type. For those taking chlorthalidone vs other medications, the risk of developing FG levels higher than 125 mg/dL (6.9 mmol/L) is modestly greater, but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events.

Elevated fasting glucose levels predicts IGT and diabetes also in middle-age subjects

To add to the discussion whether higher normal range fasting plasma glucose levels or ”IFG” may be able to predict the risk to develop type 2 diabetes we tested in 294 healthy middle-age persons during a mean follow up time of 3.8 years which range of fasting glucose levels allowed to predict type 2 diabetes. A significant increase in frequency of IGT/diabetes was significantly observed for the ”IFG” category. We therefore conclude that elevated fasting glucose levels in the ”IFG” category predict the development of IGT/diabetes in a middle-age population.

Prevalence of the metabolic syndrome in elementary school children

To determine the prevalence of the metabolic syndrome (MS) and its related components in elementary-aged school children. Three hundred and seventy-five 7-9-y-old boys (n=182) and girls (n=193) in the eastern Kansas area served as participants. Criteria for the MS were the presence of three or more of the following components: 1) central obesity (waist circumference>or=90th percentile in males and females); 2) elevated triglyceride concentrations (>or=1.13 mmol/l); 3) low HDL-C concentrations (<or=1.04 mmol/l in males and females); 4) elevated blood pressure (systolic and/or diastolic>or=90th percentile, age and gender specific); or 5) elevated fasting glucose levels (>or=6.10 mmol/l). The prevalence of the MS in this sample was 5%, and was similar across gender and race. Fifty percent of the children had no components and 15% had at least two components, with elevated blood pressure the most common component (37%). The MS is prevalent even in young children at rates similarly reported in adolescents.

Sex differences in the relation of depressive symptoms, hostility, and anger expression to indices of glucose metabolism in nondiabetic adults.

This study examined the relation of depressive symptomatology, hostility, and anger expression to indices of glucose metabolism and tested whether gender moderates these associations in a sample of 135 healthy, nondiabetic adults (75 men, 60 women). The severity of depressive symptoms, hostility, and anger expression was positively associated with estimated insulin resistance (IR) and insulin in women but not in men. Anger expression was positively associated with glucose in women only. A summary score of depressive symptoms, hostility, and anger expression was positively associated with estimated IR, insulin, and glucose in women but not in men. Hence, in women, IR and elevated levels of fasting insulin and glucose may be one pathophysiological mechanism mediating the increased risk of cardiovascular disease and Type 2 diabetes associated with these psychological attributes.

Vascular Structure and Function in Women: Relationship with Body Mass Index

The purpose of the present study was to compare endothelial function in lean (body mass index [BMI]=18.0-24.9 kg/m2); overweight (BMI=25-29.9 kg/m2); and obese (BMI>30 kg/m2), healthy, eumenorrheic women. Eighteen lean, 22 overweight, and 19 obese eumenorrheic middle-aged women were studied. Vascular structure and function were assessed via non-invasive ultrasound imaging of the carotid and brachial arteries. Body composition, blood pressure, fasting blood lipids, glucose, and insulin also were measured. The groups demonstrated significantly (p<0.001) different mean values for total body, lean body, and fat masses. The obese group demonstrated significantly (p<0.05) elevated fasting glucose and insulin levels and lower high-density lipoprotein levels as compared to the lean group. The overweight group also demonstrated elevated fasting glucose levels as compared to the lean group (p<0.05) with no significant difference from the obese group. Only systolic blood pressure differed among the three groups, being elevated in the obese group compared to the lean group (p<0.05). The obese group demonstrated significantly (p<0.05) elevated carotid artery lumen diameter, carotid artery wall cross-sectional area, and brachial artery lumen diameter with significantly (p<0.05) lower flow-mediated dilation as compared to the lean group. The overweight group demonstrated elevated carotid artery wall cross-sectional area and brachial artery lumen diameter as well as lower flow-mediated dilation as compared to the lean group (p<0.05). The results of this study support the hypothesis that carotid artery wall cross-sectional area is elevated and flow-mediated dilation reduced in overweight and obese eumennorheic women as compared to lean counterparts in relation to BMI classification.

A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics

Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist–hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.

IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and gestational diabetes

Maturity-onset diabetes of the young (MODY) is a monogenic autosomal-dominant form of diabetes mellitus with onset before 25 years of age. Genetic variation in insulin promoter factor-1 ( IPF1) (MODY4) is uncommon but may contribute to early- or late-onset diabetes as part of a polygenic background. IPF1 is a homeodomain transcription factor required for pancreas development. Our aim was to identify whether IPF1 gene mutations play a role in Italian early-onset type 2 diabetic (T2D) patients and what functional impact mutations may have in the beta cell. We screened 40 Italian early-onset type 2 diabetic probands for IPF1 mutations, performed oral glucose tolerance tests in the unaffected family members, and performed in vitro functional studies of the mutant variant. In an extended family (Italy-6) of 46 members with clinical phenotypes of gestational diabetes, MODY, and T2D, a single nucleotide change of CCT to ACT was identified at codon 33 resulting in a Pro to Thr substitution (P33T) in the IPF1 transactivation domain that also contributes to an altered metabolic status in the unaffected NM subjects. Of the 22 genotyped Italy-6 members, 9 carried the P33T allele (NM), of whom 5 have either T2D or elevated fasting glucose levels. Oral glucose tolerance tests showed higher glucose levels at 90 minutes in unaffected NM compared with unaffected NN subjects. Of the 5 female pregnant carriers of the IPF1 mutation, 4 had pregnancies complicated by reduced birth weights, miscarriages, or early postnatal deaths. In studies in vitro, the IPF1 mutant protein (P33T) showed a reduction in DNA-binding and transcriptional activation functions as compared to the wild-type IPF1 protein. Our findings suggest that the P33T IPF1 mutation may provide an increased susceptibility to the development of gestational diabetes and MODY4 in the Italy-6 pedigree.

Altered Metabolic Profiles among Older Mothers with a History of Preeclampsia

Preeclampsia has been linked to increased risk for cardiovascular disease and, more recently, to reduced risk for breast cancer later in life. The altered chronic disease risk associated with prior preeclampsia may reflect underlying metabolic differences. In this case-control study, we examined the metabolic profiles of older mothers with and without a history of preeclampsia in their first pregnancies. At the time of the study, subjects were non-pregnant, non-smoking women who completed their first pregnancies at age 30 or older, were pre-menopausal, and were free of serious chronic disease. Cases were 13 women who experienced preeclampsia in their first pregnancies; controls were 13 women with uncomplicated first pregnancies, frequency matched to cases on race/ethnicity, current age, and age at delivery. A fasting blood sample was collected from each subject during the luteal phase (day 19–22) of the menstrual cycle and assayed for specific factors thought to be linked to hypertensive disease or breast cancer. Compared to women with uncomplicated pregnancies, those with a history of preeclampsia had significantly elevated levels of fasting serum triglycerides, insulin and glucose, and a higher fasting insulin resistance index, suggesting that women with prior preeclampsia were relatively insulin resistant. In addition, cases had higher levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) and a higher molar ratio of IGFBP-3 to IGF-1 than did controls. Adjustment for obesity and other potential confounders did not appreciably alter the magnitude of these associations. This preliminary study suggests that women with a history of preeclampsia have persistent metabolic abnormalities consistent with their observed excess risk for cardiovascular morbidity and mortality, and their apparent reduced risk for breast cancer later in life.