Maintenance Of Normal Glucose Tolerance Research Articles

295-LB: Pancreatic Peroxisomes Are Required for Physiological Regulation of Insulin Secretion and Maintenance of Normal Glucose Tolerance in Male Mice

The regulation of glucose-stimulated insulin secretion (GSIS) is central to maintenance of glucose disposal. The role of lipid storage and lipid oxidation to regulate pancreatic islet β-cell insulin secretion is not completely understood. Peroxisomes are enriched in insulin-producing β-cells, but their contribution to β-cell function and maturity is lacking. Therefore, we generated a novel model of peroxisomal dysfunction to test the hypothesis that peroxisomal lipid metabolism is required to prevent a hyperlipidemic environment that interferes with β-cell function and maturity. Pex5 plays a critical role in importing the majority of peroxisomal proteins into the peroxisomal matrix; thus, deletion of the Pex5 gene creates a cellular environment with reductions in function of this organelle. In this study, we bred Pex5 mice on a C57BL/6J background containing ‘floxed’ alleles to Pdx1-cre mice to generate offspring with a pancreas-wide deficiency in Pex5 expression and abundance. Glucose tolerance was impaired by 12 weeks in male mice (n=20; AUC p<0.05). Surprisingly, GSIS was elevated in Pex5Pdx1-/- mice compared to littermate controls both in vivo (n=15; AUC p<0.05) and ex vivo in isolated islets as measured by perifusion analysis (n=12; AUC p<0.01). We further found that a subset of β-cells from Pex5Pdx1-/- mice expressed the de-differentiation marker Aldh1a3, while a subset of β-cells showed reductions in MafA and Nkx6.1 staining compared to controls. Perilipin-1 staining showed increased presence of lipid droplets in pancreatic tissue of Pex5Pdx1-/- mice versus controls. Thus, pancreatic deletion of peroxisomal function results in increased lipid storage in pancreatic tissue that is correlated with exaggerated insulin secretion. Collectively, these data are in support of a model whereby peroxisomal function supports β-cell insulin secretion and maintenance of the fully differentiated state. Disclosure S. Burke: None. S. Ghosh: None. D. Burk: None. R. Noland: None. J. Collier: None.

Enhanced \u03b2-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110\u03b1 inactivation in adipose tissue

The insulin/IGF-1 signalling pathway is a key regulator of metabolism and the rate of ageing. We previously documented that systemic inactivation of phosphoinositide 3-kinase (PI3K) p110α, the principal PI3K isoform that positively regulates insulin signalling, results in a beneficial metabolic effect in aged mice. Here we demonstrate that deletion of p110α specifically in the adipose tissue leads to less fat accumulation over a significant part of adult life and allows the maintenance of normal glucose tolerance despite insulin resistance. This effect of p110α inactivation is due to a potentiating effect on β-adrenergic signalling, which leads to increased catecholamine-induced energy expenditure in the adipose tissue. Our findings provide a paradigm of how partial inactivation of an essential component of the insulin signalling pathway can have an overall beneficial metabolic effect and suggest that PI3K inhibition could potentiate the effect of β-adrenergic agonists in the treatment of obesity and its associated comorbidities.

Role of chromium compounds in diabetes

Diabetes Mellitus is a complex disease where the carbohydrate, protein and fat metabolism is deranged and co-exists with insulin resistance. The defect is either in the secretion of insulin, in the insulin receptors or post receptor events1. It manifests as hyperglycemic state with dyslipidemia and other metabolic defects. Insulin promotes glucose uptake through its receptor located in the cell surface by generating signal that results in the translocation of glucose transporter (GLUT) to cell surface. Thereafter, glucose is transported to the cytoplasm through these receptors by facilitated diffusion in the muscle cell and the adipose tissues. In type 2 DM, the muscle cells and adipose tissues are resistant to this signaling pathway2–7. Trivalent chromium (Cr) vital micronutrient obtained from diet which serves to potentiate insulin action and maintenance of normal glucose tolerance. Studies suggest, chromium is an essential cofactor that is required for optimum insulin activity9–11. Cr increases insulin receptor numbers8 on cell surface of the target cells hence facilitates more insulin-receptor binding. Trivalent Cr, especially Cr tri-picolinate and chromium histidinate are effective in insulin resistance. Chromium replacement is essential in deficient conditions and this fact has been well established, the aim of this review is to assess the role of chromium in the pathology of diabetes.

EFFECTS OF CHROMIUM ON PROTEIN AND CARBOHYDRATE LEVELS IN THE MANTLE OF FRESHWATER MUSSEL Anodonta woodiana (Lea, 1834)

<p>Chromium is one of the technical importance metals found in the aquatic environment at increasing concentrations, resulting from metallurgic, refractory, chemical, and tannery in­dustries (Satyaparameshwar et al., 2006). The metal is known to be essential for all animals such as maintenance of normal glucose tolerance (Chassard-Bouchaud et al., 1989). It also involves in metabolisms of lipids, proteins, nucleic acids, and mineral substances (Pechova & Pavlata 2007). At elevated concentrations, chromium is toxic to mussels, resulting in changes of mRNA expression, immunomodulation, DNA stability, and stress response path­ways (Franzellitti et al., 2012). Swan mussels (Anodonta woodiana) living at the interface of the free-flowing water and the sediment phase of many lotic freshwater ecosystems are known to accumulate metals in their body. Mussels require carbohydrates as main energy source for their metabolic processes (Honkoop et al., 1999). Proteins are also required by mussels for catalyzing biochemical reactions, transport and storage of molecules in and out, or within cells, and have structural and mechanical functions (Albert et al., 1994). Proteins and carbohydrates are also important components in the shell formation (Marie et al., 2007; Marin & Luquet 2004). Mantle secretes proteins and carbohydrates into extra pallial fluid, which is directly adjacent to the shell. The objective of this research was to study the effects of Cr on the protein and carbohydrate levels in the mantle of A. woodiana.</p>

Hidden metabolic disturbances in women with normal glucose tolerance five years after gestational diabetes.

Background. The study aimed to assess whether women with prior gestational diabetes (pGDM), despite maintenance of normal glucose tolerance (NGT) five years after delivery, display metabolic disturbances compared to healthy controls. Methods. 45 pGDM with NGT were compared to 18 women without a history of GDM (CON), matched for age (37.0 ± 4.1 versus 35.2 ± 5.3, P = ns) and BMI (24.3 ± 3.1 versus 23.3 ± 3.3, P = ns). Metabolic parameters were derived from oral and intravenous glucose tolerance tests; furthermore lipid profile, C-reactive protein (CRP), adiponectin, leptin, and glucagon were assessed. Results. Five years postpartum, pGDM had increased glucose concentrations during the OGTT (AUC: 1.12 ± 0.15 versus 1.0 ± 0.12 mol/L ∗ min, P = 0.003) and insulin sensitivity was decreased compared to CON (OGIS: 467.2 ± 64.1 versus 510.6 ± 53.1 mL/min ∗ m2, P = 0.01). pGDM had lower adiponectin (8.1 ± 2.6 versus 12.6 ± 5.3, P < 0.008) but increased waist circumference and CRP compared to CON. Conclusions. Despite diagnosis of normal glucose tolerance, pGDM are characterized by hyperglycemia and insulin resistance compared to healthy controls, accompanied by decreased adiponectin and increased CRP concentrations, thus linking metabolic disturbances to an increased cardiovascular risk in pGDM.

Pathophysiology of diabetes mellitus type 2: beyond the duo "insulin resistance-secretion deficit".

T2DM involves at least two primary pathogenic mechanisms: (a) a progressive decline in pancreatic islet cell function resulting in reduced insulin secretion and (b) peripheral insulin resistance resulting in a decrease in the metabolic responses to insulin. This dynamic interaction between insulin secretion and insulin resistance is essential to the maintenance of normal glucose tolerance (NGT). The transition from the normal control of glucose metabolism to type 2 diabetes mellitus occurs through the intermediate states of altered metabolism that worsen over time. The first state of the disease is known as prediabetes, and consists of a set of metabolic disorder characterized by a great hyperglycemia, enough to increase of retinopathies, nephropathies and neuropathies incidence. If we advance in the T2DM temporal sequence we found a remarkable change in the pancreatic cells population that form the Langerhans islets, mainly caused by amylin fibers accumulation over these cells from polypeptide hormone called amyloid polypeptide or IAPP. The IAPP hypersecretion and amylin fibers deposition attached to the endoplasmic reticulum stress caused by excessive workload due to biosynthesis overproduction of insulin and IAPP result in ?-cell apoptosis. In addition to these alterations, we must also consider the changes observed in incretins profiles like GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1) directly related to glucose homeostasis maintenance. Risk factors that predispose to a healthy individual to develop T2DM are several, but the most important is the obesity. The body mass index (BMI) has been used in numerous epidemiological studies as a powerful indicator of T2DM risk. Lipotoxicity caused by circulating free fatty acids increased, changes in lipoprotein profiles, body fat distribution and glucotoxicity caused by cells over-stimulation are other risk factors to consider in T2DM developing.

Predictive values of serum insulin kinetics for reversion of impaired glucose tolerance to normal glucose tolerance and the effects of voglibose treatment: a retrospective post hoc analysis of a Japanese phase III study

In a phase III study, voglibose was shown to reduce the risk of development of type 2 diabetes mellitus (T2DM) by 40.5 % in Japanese individuals with impaired glucose tolerance (IGT), and appeared to promote reversion of IGT to normal glucose tolerance (NGT). In a retrospective, post hoc analysis, data from this study, plus follow-up findings from subjects who achieved NGT during the study and who were off-treatment, were analyzed to investigate serum insulin kinetic parameters which might be predictors of IGT reversion to NGT, and maintenance of NGT once achieved. The effects of voglibose on serum insulin kinetics in individuals with IGT were also assessed. Subjects with IGT (n = 1778) were randomized to receive voglibose (0.6 mg/day) or placebo for a mean of 48.1 weeks. During treatment, 1053 subjects achieved NGT, 569 continued to have IGT, and 156 developed T2DM. Analysis of baseline characteristics in each outcome group showed that subjects with higher 30-min serum immunoreactive insulin (IRI) levels in a 75 g oral glucose tolerance test (OGTT) or higher insulinogenic indexes at baseline were more likely to achieve NGT, whether they received voglibose or placebo. Among subjects who achieved NGT, the mean increase in OGTT 30-min IRI level from baseline to endpoint was significantly greater after treatment with voglibose than with placebo. Individuals who had higher OGTT 30-min IRI levels when achieving NGT seemed more likely to sustain this state. Thus, insulin secretion kinetics appeared to predict reversion of IGT to NGT and maintenance of NGT once achieved.

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women

High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

Chromium, Exercise, and Body Composition

Chromium is an essential trace element involved in the metabolism of carbohydrates, lipids, and proteins mainly by increasing the efficiency of insulin. Chromium deficiency affects the maintenance of normal glucose tolerance and healthy lipid profiles. The Estimated Safe and Adequate Daily Dietary Intake for chromium is 50 to 200 µg/d for adults. However, the dietary intake of chromium in humans is often suboptimal. Chromium assessment has proven to be a challenge due to the low amounts of chromium present in biological materials and the absence of a reliable indicator of chromium status. Recently, chromium has been touted as an agent for increasing lean body mass and decreasing percent body fat. This article reviews the various studies that have been conducted to investigate the relationship of chromium with exercise and body composition.

Preliminary studies on the inorganic constituents of some indigenous hypoglycaemic herbs on oral glucose tolerance test

Medicinal herbs used in indigenous medicines in crude forms for the management of diabetes mellitus, contain both the organic and inorganic constituents. It is known that certain inorganic mineral elements (potassium, zinc, calcium, traces of chromium, etc.) play an important role in the maintenance of normal glucose-tolerance and in the release of insulin from β cells of islets of Langerhans. In the present study, 30 hypoglycaemic herbs were selected from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. Special emphasis was given to their inorganic parts by carefully preparing ash (which contains mainly mineral elements) of the specific parts of the herbal samples under study. Next, the single dose effect on the oral glucose tolerance test (GTT) was studied using previously fasted albino rats. Similar effects were also compared with their organic parts of the concerned herbal samples in the form of 95% ethanolic extracts. In certain inorganic samples, more pronounced action (as glucose tolerance factor) were noticed than their corresponding organic parts.

Reciprocal variations in insulin-stimulated glucose uptake and pancreatic insulin secretion in women with normal glucose tolerance.

Maintenance of normal glucose tolerance is achieved in subjects with a wide range of insulin sensitivity. It follows, therefore, that the body must possess a sensor mechanism that assesses the body's sensitivity to insulin and appropriately adjusts the secretion of insulin to maintain normal glucose homeostasis. We evaluated the relation between insulin action and insulin secretion. Euglycemic hyperinsulinemic clamp (1 mU/kg.minute) and hyperglycemic clamp (+125 mg/dL) studies were performed in 32 non-obese women with normal oral glucose tolerance tests. The subjects were stratified into quartiles based upon their insulin-mediated rate of glucose uptake during the euglycemic insulin clamp. Total body glucose disposal varied threefold, ranging from 4.00 to 11.18 mg/kg.minute. A significant inverse relation (r = -0.50, P < .01) was noted between the rate of total body insulin-mediated glucose disposal (insulin clamp) and the total plasma insulin response during the hyperglycemic clamp. Women in the lowest quartile of insulin sensitivity (mean glucose uptake 5.07 +/- 0.20 mg/kg.minute) had the highest plasma insulin response during the hyperglycemic clamp (109 +/- 20 microU/mL). In contrast, women in the highest quartile of insulin sensitivity (glucose uptake 9.90 +/- 0.38 mg/kg.minute) had the lowest plasma insulin response during the hyperglycemic clamp (55 +/- 16 microU/mL; P < .001 versus the lowest quartile). These results demonstrate that among subjects with normal glucose tolerance, there exists a large variation in both insulin-mediated glucose uptake and pancreatic insulin secretion. Nonetheless, normal glucose tolerance is maintained because of a finely regulated balance, which couples the demand for insulin secretion by the pancreatic beta cells to the level of whole-body insulin sensitivity.

Prevention of diabetes mellitus in non-obese diabetic mice by Linomide, a novel immunomodulating drug

Oral administration of the synthetic immunomodulating drug quinoline-3-carboxamide (Linomide) in the drinking water to 5-week-old female non-obese diabetic (NOD) mice resulted in complete protection from insulitis and maintenance of normal glucose tolerance for over 40 weeks (impaired glucose tolerance: treated n = 2 of 18; control n = 17 of 18, p < 0.0001). Delayed administration of the drug at 16 weeks resulted in slowing of the progression to diabetes when assessed at 42 weeks (treated with diabetes n = 7 of 25; control with diabetes 25 of 43, p < 0.0234). No gross changes of immune system cell phenotype or function were observed in the Linomide-treated group. Adoptive transfer of spleen and lymph node cells from treated female NOD mice into sub-lethally irradiated male recipients failed to transfer diabetes, whereas a similar transfer of cells obtained from untreated age-matched controls resulted in diabetes in all secondary recipients (diabetes in control group n = 12 of 13; in Linomide group n = 0 of 11, p < 0.0001). Linomide pretreatment of the secondary recipients also inhibited the transfer of diabetes (diabetes in pretreated group n = 2 of 9, control group n = 12 of 13, p < 0.015), as did adoptive co-transfer of cell mixtures obtained from treated female NOD mice, free of diabetes, and from diabetic NOD female mice (diabetes in Linomide group n = 4 of 9; in control group 7 of 7, p < 0.0337).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of diabetes mellitus in non-obese diabetic mice by Linomide, a novel immunomodulating drug

Oral administration of the synthetic immunomodulating drug quinoline-3-carboxamide (Linomide) in the drinking water to 5-week-old female non-obese diabetic (NOD) mice resulted in complete protection from insulitis and maintenance of normal glucose tolerance for over 40 weeks (impaired glucose tolerance: treated n=2 of 18; control n=17 of 18, p<0.0001). Delayed administration of the drug at 16 weeks resulted in slowing of the progression to diabetes when assessed at 42 weeks (treated with diabetes n=7 of 25; control with diabetes 25 of 43, p<0.0234). No gross changes of immune system cell phenotype or function were observed in the Linomide-treated group. Adoptive transfer of spleen and lymph node cells from treated female NOD mice into sub-lethally irradiated male recipients failed to transfer diabetes, whereas a similar transfer of cells obtained from untreated age-matched controls resulted in diabetes in all secondary recipients (diabetes in control group n=12 of 13; in Linomide group n=0 of 11, p<0.0001). Linomide pretreatment of the secondary recipients also inhibited the transfer of diabetes (diabetes in pretreated group n=2 of 9, control group n=12 of 13, p<0.015), as did adoptive co-transfer of cell mixtures obtained from treated female NOD mice, free of diabetes, and from diabetic NOD female mice (diabetes in Linomide group n=4 of 9; in control group 7 of 7, p<0.0337). Our data indicate that Linomide-treated NOD mice generate immune cells with the capacity to downregulate responses to beta-cell antigens, apparently through immunoregulation rather then antigen non-specific immunosuppression. Based on our findings and considering the lack of severe side effects of orally administered Linomide in man, this new compound should be considered as a potential drug for treatment of insulin-dependent diabetes mellitus.

3 Action of insulin on glucose metabolism in vivo

Insulin plays a key role in the maintenance of normal glucose tolerance by suppressing endogenous glucose production during a meal. Insulin is not, however, involved in the regulation of splanchnic glucose uptake. The latter process appears, based on studies performed in dogs, to be regulated primarily by the arterial-portal glucose gradient and to a smaller extent by glucose mass-action. Regarding peripheral glucose utilization, insulin is not needed to maintain a normal rate of glucose utilization since this can also be achieved by hyperglycaemia and glucose mass-action. Insulin is, however, necessary for the maintenance of normal rates of glucose oxidation and storage in insulin-sensitive tissues, and for the prevention of excessive gluconeogenic substrate production.

The disposal of an oral glucose load in patients with non-insulin-dependent diabetes

Following glucose ingestion, tissue glucose uptake is enhanced and endogenous glucose production is inhibited, thus contributing to the maintenance of normal glucose tolerance. To examine whether these responses are disturbed in diabetes, glucose kinetics after oral glucose administration were studied in 12 non-insulin-dependent diabetic and 10 age- and weight-matched control subjects. A double tracer approach was used, whereby the endogenous glucose pool was labeled with 3- 3H-glucose and the oral load with 1- 14C-glucose. The two glucose tracers were separated in plasma by a two-step chromatographic procedure, and the two sets of isotopic data were analyzed according to a two-compartment model for the glucose system. Basally, glucose production was slightly higher in diabetics than in controls (2.51 ± 0.24 v 2.28 ± 0.11 mg/kg · min, NS) even though the former had higher plasma glucose (189 ± 19 v 93 ± 2 mg/dL, P < .001) and insulin (23 ± 4 v 12 ± 1 μU/mL, P < .05) concentrations. Following the ingestion of 1 g/kg of glucose, oral glucose appeared in the peripheral circulation in similar time-course and amount in the two groups (75 ± 2% of the load over 3.5 hours in the diabetics v 76 ± 3% in controls). Endogenous glucose production was promptly inhibited in diabetic and normal subjects alike, but the mean residual hepatic glucose production after glucose ingestion was significantly greater in the diabetic group (17 ± 2 v 10 ± 3 g/3.5 h, P < .05). At the end of the 3.5-hour study period, hepatic glucose production was still partially suppressed in both groups (by about 50%). This impairment in suppression of hepatic glucose production in the diabetics occurred despite the presence of marked hyperglycemia (mean plasma glucose following glucose ingestion = 298 ± 23 v 147 ± 7 mg/dL in controls, P < .001) and similar plasma insulin concentrations (46 ± 10 v 60 ± 7 μU/mL, NS). In the diabetics, endogenous glucose production was directly correlated with plasma glucose concentration both basally ( r = .92, P < .001) and after glucose ( r = .63, P < .05). At the end of 3.5 hours the healthy subjects had disposed of 60 ± 4 g by tissue uptake; this amount represented nearly 100% of the glucose (both oral and endogenous) that had appeared in the peripheral circulation. In contrast, in the diabetics tissue glucose disposal was only 44 ± 4 g over 3.5 hours ( P < .05 v controls); 11 ± 3 g were lost into the urine and 16 ± 3 g had accumulated in the glucose space. In the diabetic group the mean plasma glucose concentration postload was inversely correlated with tissue glucose disposal ( r = −.70, P < .01). We conclude that, in non-insulin-dependent diabetic patients: (1) the peripheral appearance of an ingested glucose load follows a normal pattern; (2) suppression of endogenous glucose production after oral glucose ingestion is impaired when compared with controls despite a twofold higher plasma glucose concentration and comparable plasma insulin levels; (3) tissue uptake of oral and endogenous glucose is markedly impaired; and (4) reduced tissue glucose uptake and relative overproduction of glucose by the liver both contribute to postprandial hyperglycemia.

Role of Liver in Glucose Homeostasis

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes.

Chromium Deficiency During Total Parenteral Nutrition

Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.

Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus

Through the use of a double-blind cross-over investigative method, the effect of trivalent chromium supplements on blood sugar concentrations of normal and diabetic human subjects was evaluated. Four normal and 10 diabetic subjects took 50 μg. of trivalent chromium and a chromium-placebo thrice daily by mouth for 16-week periods. Chromium did not improve hyperglycemia in diabetic patients, and there was no difference in diabetic glucose tolerance measured after placebo and chromium treatment. Normal glucose tolerance was also unaffected. Despite evidence that trivalent chromium may be an essential micronutrient for maintenance of normal glucose tolerance in rats, results of this investigation do not support suggestions of a similar role in man.

Effect of trivalent chromium on glucose tolerance

Trivalent chromium, an essential trace element for maintenance of normal glucose tolerance in the rat, was administered to diabetics and subjects with normal glucose utilization. Oral supplementation with 150 to 1000 μg. of chromium (III) per day for periods of 15 to 120 days was associated with an improved glucose tolerance in 3 out of 6 diabetics. Short term administration of the element was ineffective. Normal glucose tolerance was not influenced. It is suggested that in the human, as in the rat, chromium is required for optimal glucose utilization.