Changes In Glucose Regulation Research Articles

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy — A focus on energy expenditure

ObjectiveBariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. MethodsDiet-induced obese male Sprague–Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. ResultsFollowing VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. ConclusionsCollectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Effects of Dietary Carbohydrate Profile on Nocturnal Metabolism, Sleep, and Wellbeing: A Review.

Sleep is a crucial biological function and a well-established driver of health and wellbeing across the lifespan. In this review, we describe how sleep in humans is associated with specific circadian metabolic and physiological changes, and how the organization of sleep-wake states is related to regulation of nocturnal metabolism during fasting. Among the modifiable factors that can contribute to sleep-related benefits, emerging evidence suggests that diet and nocturnal changes in glucose regulation are strong determinants of sleep quality. Here, we review studies that have explored the importance of quantity and quality of dietary carbohydrates and proteins in modulation of sleep and sleep-related health benefits. Future research may guide the creation of nutritional solutions to improve sleep, which could lead to positive changes in health, wellbeing, and overall quality of life.

Functional Connectivity of the Anterior and Posterior Hippocampus: Differential Effects of Glucose in Younger and Older Adults.

The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory. Here, we probe age, glucose and human cognition with a special emphasis on resting-state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design 32 healthy adults (16 young and 16 older) ingested a drink containing 25 g glucose or placebo across two counter balanced sessions. They then underwent resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive testing. There was a clear dissociation in the effects of glucose by age. Magnitude change in rsFC from posterior hippocampus (pHPC) to medial frontal cortex (mPFC) was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants.

Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients

Diabetes occurring as a direct consequence of loss of liver function is usually characterized by non-diabetic fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels and should regress after orthotopic liver transplantation (OLT). This observational, longitudinal study investigated the relationship between the time-courses of changes in all 3 direct determinants of glucose regulation, i.e., β-cell function, insulin clearance and insulin sensitivity, and diabetes regression after OLT. Eighty cirrhotic patients with non-diabetic FPG and HbA1c levels underwent an extended oral glucose tolerance test (OGTT) before and 3, 6, 12 and 24 months after OLT. The OGTT data were analysed with a mathematical model to estimate derivative control (DC) and proportional control (PC) of β-cell function and insulin clearance (which determine insulin bioavailability), and with the Oral Glucose Insulin Sensitivity (OGIS)-2 h index to estimate insulin sensitivity. At baseline, 36 patients were diabetic (45%) and 44 were non-diabetic (55%). Over the 2-year follow-up, 23 diabetic patients (63.9%) regressed to non-diabetic glucose regulation, whereas 13 did not (36.1%); moreover, 4 non-diabetic individuals progressed to diabetes (9.1%), whereas 40 did not (90.9%). Both DC and PC increased in regressors (from month 3 and 24, respectively) and decreased in progressors, whereas they remained stable in non-regressors and only PC decreased in non-progressors. Insulin clearance increased in all groups, apart from progressors. Likewise, OGIS-2 h improved at month 3 in all groups, but thereafter it continued to improve only in regressors, whereas it returned to baseline values in the other groups. Increased insulin bioavailability driven by improved β-cell function plays a central role in favouring diabetes regression after OLT, in the presence of a sustained improvement of insulin sensitivity. Diabetes occurring in cirrhosis as a direct consequence of loss of liver function should regress after transplantation of a new functioning liver, though the pathophysiological mechanisms are unclear. This is the first study evaluating the contribution of all 3 direct determinants of insulin-dependent glucose regulation using a sophisticated mathematical model. Results show that β-cell function is the key process governing favourable or detrimental changes in glucose regulation in cirrhotic patients undergoing transplantation, pointing to the need to develop therapies to sustain β-cell function in these individuals. ClinicalTrials.gov, NCT02038517.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

ObjectiveTo detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. MethodsBlood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). ResultsBlood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l-1; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). ConclusionGlucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia.

Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined.We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters.Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice.We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids.

Soda Consumption during Ad Libitum Food Intake Predicts Weight Change

Soda consumption may contribute to weight gain over time. Objective data were used to determine whether soda consumption predicts weight gain or changes in glucose regulation over time. Subjects without diabetes (128 men, 75 women; mean age 34.3±8.9 years; mean body mass index 32.5±7.4; mean percentage body fat 31.6%±8.6%) self-selected their food from an ad libitum vending machine system for 3 days. Mean daily energy intake was calculated from food weight. Energy consumed from soda was recorded as were food choices that were low in fat (<20% of calories from fat) or high in simple sugars (>30%). Food choices were expressed as percentage of daily energy intake. A subset of 85 subjects had measurement of follow-up weights and oral glucose tolerance (57 men, 28 women; mean follow-up time=2.5±2.1 years, range 6 months to 9.9 years). Energy consumed from soda was negatively related to age (r=−0.27, P=0.0001) and choosing low-fat foods (r=-0.35, P<0.0001), but positively associated with choosing solid foods high in simple sugars (r=0.45, P<0.0001) and overall average daily energy intake (r=0.46, P<0.0001). Energy intake from food alone did not differ between individuals who did and did not consume beverage calories (P=0.11). Total daily energy intake had no relationship with change in weight (P=0.29) or change in glucose regulation (P=0.38) over time. However, energy consumed from soda correlated with change in weight (r=0.21, P=0.04). This relationship was unchanged after adjusting for follow-up time and initial weight. Soda consumption is a marker for excess energy consumption and is associated with weight gain.

Changes in Insulin Secretion and Action in Adults With Familial Risk for Type 2 Diabetes Who Curtail Their Sleep

OBJECTIVEExperimental sleep deprivation is accompanied by changes in glucose regulation. However, the effects of chronic sleep insufficiency on insulin secretion and action in populations at high risk for type 2 diabetes are not known. This study examined the relationship between objectively documented habitual sleep curtailment and measures of insulin sensitivity, insulin secretion, and oral glucose tolerance in free-living adults with parental history of type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 47 healthy participants with parental history of type 2 diabetes (26 female/21 male, mean [SD] age 26 [4] years and BMI 23.8 [2.5] kg/m2) completed 13 (SD = 2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. Indices of diabetes risk based on oral glucose tolerance tests were compared between participants with habitual short sleep and those with usual sleep duration >6 h/day.RESULTSConsistent with a behavioral pattern of habitual sleep curtailment, short sleepers obtained an average of 1.5 h less sleep per night and showed signs of increased sleep pressure. Participants who habitually curtailed their sleep had considerably higher indices of insulin resistance and increased insulin secretion but maintained normal glucose tolerance similar to that of subjects who slept more.CONCLUSIONSYoung lean adults with parental history of type 2 diabetes who habitually curtail their sleep have increased insulin resistance and compensatory hyperinsulinemia—a pattern that has been associated with higher risk of developing diabetes in such susceptible individuals.

Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports

Although there are several case reports in literature linking use of antidepressants and disturbances in glucose control, it is difficult to identify risk factors for serious adverse drug events from individual case reports. The aim of this review is to provide a descriptive analysis of the demographic and clinical characteristics of published glucose dysregulation case reports following initiation of antidepressant agents. Published case reports of glucose dysregulation associated with antidepressants were accessed through PubMed (Medline), PsycINFO, and Web of Science (WOS) between January 1, 1970 and April 30, 2010. The following key words were used: antidepressant agents, glucose dysregulation, hypoglycemia, hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. Case reports were excluded if glucose dysregulation occurred after a drug overdose/improper dosing or after the patient was prescribed drugs known to cause glucose disturbances in addition to antidepressant agents. Out of the 17 cases reports reviewed, nine (53%) were of hyperglycemia while eight (47%) were of hypoglycemia. Hyperglycemia was reported following treatment with clomipramine, fluvoxamine, imipramine, mianserin, mirtazapine, paroxetine, and sertraline. Hypoglycemia was reported following treatment with doxepine, fluoxetine, imipramine, nefazodone, nortriptyline, maprotiline, and sertraline. Fourteen out of the seventeen patients were female (82%) while ten had a history of diabetes mellitus (59%). The average age of the patients was 53.9 (SD = 17.5) years (range: 24-84 years). The time to onset of glucose dysregulation ranged from 4 days to 5 months after initiation of antidepressant therapy. More than two-thirds (68%) of the cases (n = 11) reported glucose control disturbances within 1 month of therapy. It is not clear from published case reports whether changes in glucose regulation, following antidepressant therapy initiation are due to antidepressants or changes in mood and lifestyle. Nonetheless, healthcare providers should be aware of the potential changes in glucose regulation especially in the first month of antidepressant therapy, and use appropriate clinical and laboratory monitoring to prevent serious adverse events in patients at risk.

Chronic Sleep Disturbance Impairs Glucose Homeostasis in Rats

Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control.

Glucose dysregulation among veterans living with schizophrenia-related disorders after switching second-generation antipsychotics

To compare (1) blood glucose and glycosylated hemoglobin (A1C) laboratory results and (2) longitudinal trends in blood glucose levels among veterans switched from one second-generation antipsychotic (SGA) to another. Retrospective, naturalistic, nonequivalent control group. United States between April 1, 2003, and September 30, 2003. 1,776 U.S. Veterans Health System beneficiaries living with schizophrenia-related disorders switching (1) from olanzapine to another SGA, (2) to olanzapine from another SGA, and (3) among nonolanzapine SGAs. Data were retrieved from the laboratory results (LAR) database for a maximum of 180 days before and 365 days after the index date. Mean blood glucose, A1C, and change in blood glucose. Blood glucose (36.0 mg/dL, paired t test109 = -4.87, P < 0.001) and A1C (1.0%, paired t143 = -4.84, P < 0.001) declined among veterans switched from olanzapine who were taking a blood glucose-lowering agent before the switch but was unchanged for those who were not. Adjusting for age, gender, and race, addition of the switch-type variables improved prediction of blood glucose change (F-ratio = 3.76, P = 0.03). Linear mixed-effects models confirmed that blood glucose levels declined for veterans switched from olanzapine with glucose dysregulation before the switch (Est(beta2 - beta1) = -34.5 mg/dL, t424 = -5.05, P < 0.001). Blood glucose and A1C were significantly improved among veterans switched from olanzapine with evidence of glucose dysregulation before the switch. They were stable among those without evidence of preexisting glucose dysregulation. Therapeutic switches from one SGA to another should be monitored as a risk factor for changes in glucose regulation.

Studies Close In on Diabetes, Psychiatric Illness Link

Studies Close In on Diabetes, Psychiatric Illness Link

Atypical antipsychotic-associated changes in glucose regulation

Atypical antipsychotic-associated changes in glucose regulation

Age- and dose-dependent glucose-induced increases in memory and attention in schizophrenia

Glucose is the principal energy substrate for the brain, and alterations in glucose availability can alter neuronal function, including cognitive performance. Investigators have previously demonstrated glucose-induced memory and attentional improvements in humans, including a previous report from this group in subjects with schizophrenia. However, the age- and dose-dependence of this effect in schizophrenia has not been addressed. This within-subjects, double-blind experiment evaluated the cognitive effects of placebo-controlled, multiple fixed-dose oral glucose administration (0 g, 25 g, 50 g, 75 g) in younger and older patients with schizophrenia ( n=20) and healthy age-matched controls ( n=20). Each dose condition was administered on a different morning after a 9-h fast, with cognitive testing and plasma sampling following dose administration on each day. Older patients demonstrated dose-dependent improvements in recall performance on a spatial delayed response task and reaction time on a delayed match to sample task, while younger patients had decreases in attentional performance at the 75-g dose compared to placebo. As in previous reports, patients demonstrated higher plasma glucose and insulin concentrations than controls in response to fixed glucose dosing. The results provide further evidence that glucose and/or insulin can regulate brain functions relevant to memory and attention, and suggest that systemic changes in glucose regulation in schizophrenia deserve further study.

Psychological Factors Affecting Physical Condition: Endocrine Disease Literature Review

Research exploring the relationship between psychological factors and the onset, exacerbation, and perpetuation of endocrine diseases has focused primarily on three diseases: diabetes mellitus (DM), Graves' disease, and Cushing's disease. There is insufficient evidence to support the position that psychological factors directly affect the onset of DM. Recent laboratory studies suggest that stress is associated with changes in glucose regulation in a subset of diabetic patients and that temperament and coping strategies influence glycemic control in diabetic children and adolescents. Relaxation training may improve blood glucose control in non-insulin-dependent DM patients. There is no good evidence that psychological characteristics affect the development and course of thyroid disorder or Cushing's disease. Recommendations are made for future research.