Glucose Intolerance In Patients Research Articles

Adipocyte Subpopulations Mediate Growth Hormone-induced Lipolysis and Glucose Tolerance in Male Mice.

In adipose tissue, growth hormone (GH) stimulates lipolysis, leading to an increase in plasma free fatty acid levels and a reduction in insulin sensitivity. In our previous studies, we have found that GH increases lipolysis by reducing peroxisome proliferator-activated receptor γ (PPARγ) transcription activity, leading to a reduction of tat-specific protein 27 (FSP27, also known as CIDEC) expression. In previous studies, our laboratory uncovered 3 developmentally distinct subpopulations of white adipocytes. In this manuscript, we show that one of the subpopulations, termed type 2 adipocytes, has increased GH-induced signaling and lipolysis compared to other adipocyte subtypes. To assess the physiological role of GH-mediated lipolysis mediated by this adipocyte subpopulation, we specifically expressed human FSP27 (hFSP27) transgene in type 2 adipocytes (type2Ad-hFSP27tg mice). Systemically, male type2Ad-hFSP27tg mice displayed reduced serum glycerol release and nonesterified fatty acids levels after acute GH treatment, and improvement in acute, but not chronic, GH-induced glucose intolerance. Furthermore, we demonstrate that type2Ad-hFSP27tg mice displayed improved hepatic insulin signaling. Taken together, these results indicate that this adipocyte subpopulation is a critical regulator of the GH-mediated lipolytic and metabolic response. Thus, further investigation of adipocyte subpopulations may provide novel treatment strategies to regulate GH-induced glucose intolerance in patients with growth and metabolic disorders.

Extracellular volume fraction of the pancreas predicts glucose intolerance in patients undergoing major pancreatic surgeries

PurposePancreatic T1 value and extracellular volume fraction (ECV) are potential imaging biomarkers for pancreatic exocrine and endocrine function. This study aims to evaluate the ability of native T1 value and ECV of the pancreas in predicting postoperative new-onset diabetes (NODM) and worsened glucose tolerance in patients undergoing major pancreatic surgeries. MethodsThis retrospective study involved 73 patients who underwent 3 T pancreatic MRI with pre- and postcontrast T1 mapping before major pancreatic surgeries. Patients were divided into non-diabetic, pre-diabetic and diabetic groups based on their glycated hemoglobin (HbA1c) value. Preoperative native T1 value and ECV of the pancreas were compared among the three groups. The correlation of pancreatic T1 value and ECV with HbA1c was assessed by linear regression analysis, and the ability of pancreatic T1 value and ECV for predicting postoperative NODM and worsened glucose tolerance was assessed using Cox Proportional hazards regression analysis. ResultsNative pancreatic T1 value and ECV were both significantly higher in diabetic patients compared to pre-diabetic/non-diabetic patients, and ECV was also significantly higher in pre-diabetic patients compared to non-diabetic patients (all p < 0.05). Both native pancreatic T1 value and ECV showed positive correlation with preoperative HbA1c value (r = 0.50 and 0.55, respectively, both p < 0.001). ECV > 30.7% was the only independent predictor for NODM (HR = 5.687, 95% CI: 1.557, 13.468, p = 0.012) and worsened glucose tolerance (HR = 6.783, 95% CI:, 1.753, 15.842, p = 0.010) after surgery. ConclusionsPancreatic ECV predicts the risk of postoperative NODM and worsened glucose tolerance in patients undergoing major pancreatic surgeries.

Examine the Frequency of Diabetes Mellitus and Glucose Intolerance in Patients with Lichen Planus

Objective: The purpose of this study was to determine whether or not individuals with LP also had a high incidence of diabetic mellitus (DM) and/or glucose intolerance. Study Design: Cross-sectional study Place and Duration: This study was conducted at Abbottabad Medical Complex Hospital, Abbottabad in the duration from April, 2021 to October, 2021. Methods: Total 67 patients of both gender had lichen planus were presented in this study. After getting informed written consent detailed demographics of enrolled cases included age, sex, body mass index and duration of LP were recorded. Fasting blood sugar levels between 100 and 125 mg/dL (5.6 and 7.0 mmol/L) were considered to be indicative of impaired fasting glucose (IFG). Frequency of DM and glucose intolerance were recorded. SPSS 23.0 was used to analyze all data. Results: In this study, 36 (53.7%) were males and 31 (46.3%) were females. The mean age of the patients was 51.3±17.87 years and had mean BMI 26.08±12.63 kg/m2. Mean duration of LP was 3.9±10.29 years. There were 28 (41.8%) cases had classic lichen planus, followed by ashy dermatosis, hypertrophic, oral lichen planus, nail and actinic. We found that 17 (25.4%) patients had diabetes mellitus type II and 20 (29.9%) cases had glucose intolerance. We found a significant relationship between LP and DM in our cases with p value &lt;0.004. Conclusion: We concluded in this study that the patients of lichen planus had higher frequency of DM type -2 and glucose intolerance. There was a close relationship between lichen planus and DM among all cases. There is need to evaluate patients early for treatment in hospitals. Keywords: Glucose Intolerance, type-2 DM, Lichen planus

Glycemic indices at night measured by CGM are predictive for a lower pulmonary function in adults but not in children with cystic fibrosis

IntroductionIn patients with cystic fibrosis (CF), it is still unclear to which extent glucose abnormalities – preceding the diagnosis of cystic fibrosis related diabetes (CFRD) – are associated with pulmonary and nutritional outcome parameters. This study related circadian glycemic patterns to clinical outcomes in a group of CF patients not previously diagnosed with diabetes. MethodsContinuous glucose monitoring (CGM) readings (7 days) of 47 CF patients (26 children, 21 adults) with an impaired oral glucose tolerance test (OGTT) (n = 25) and/or increased Hb1Ac (> 5.5%) were analyzed. Biometric, pulmonary function and clinical parameters were retrospectively collected over a period of 1 year before (T-1) and 1 year after (T + 1) CGM (T0). Results96% (45/47) of CGM readings showed glucose values > 140 mg/dL ≥ 4.5% of the time and at least one ≥ 200 mg/dL. In the pediatric cohort, no significant associations were found between CGM parameters and pulmonary and nutritional outcome parameters. In the adult cohort, an area under the curve (AUC) > 140 mg/dL and%-time > 140 mg/dL during the night were associated with a lower forced expiratory volume in 1 s (FEV1)% predicted (pp) at time of evaluation but not with change in FEV1pp. ConclusionThis is the first study reporting the circadian glycemic pattern in children and adults at risk for CFRD. In the adult cohort an association between detection of abnormal glucose exposure and a lower FEV1pp was found. Our results support continued screening for glucose intolerance in patients with CF.

The Relationship of Resistin with Disease Severity, Inflammation and Insulin Resistance in Cirrhosis Patients

Introduction: Glucose intolerance has been shown to play an important role in the progression of early liver disease to cirrhosis. It has been suggested that insulin resistance is responsible for glucose intolerance in patients with chronic liver disease. It is thought that increased resistin through chronic inflammation in chronic liver disease may be responsible for insulin resistance. In our study, we aimed to evaluate the relationship of resistin which is released from adipose tissue with insulin resistance, inflammation markers and disease stage in patients with cirrhosis. Methods: Forty-six patients diagnosed with cirrhosis in Eskişehir Osmangazi University Faculty of Medicine, Department of Gastroenterology between March 2008 and July 2009, and 19 healthy individuals as a control group were included in the study. Patients with a diagnosis of Diabetes Mellitus, other endocrine disease or Hepatocellular Carcinoma, with fasting blood glucose above 126 mg/dl and using drugs that may affect glucose metabolism were excluded from the study. Participants with obesity were determined by skinfold thickness (biceps, triceps, suprailiac and subscapular) measurement. Statistical analyzes were performed by excluding obese patients from the study and control groups. AssayMax Human Resistin ELISA Kit was used to determine serum resistin level. The "Homaostatic Model for Insulin Resistance" (HOMA-IR) formula was used to detect insulin resistance. The studied parameters were statistically compared between the study and control groups and also between the three groups (Child Pugh stage A, B and C) formed according to the disease stage in the study group. Results: All laboratory parameters reflecting insulin resistance, inflammation markers and resistin levels were found to be significantly higher in the study group. As the Child Pugh stage advances, which is used to determine the severity and prognosis of the disease, resistin levels found higher, but it was observed that the rate of patients with decreased insulin resistance had lower levels in total fat ratio. No significant correlation was found between resistin and other markers of insulin resistance except fasting insulin level. Conclusion: In the future metabolism studies which to be performed in patients with cirrhosis detection of skinfold thickness may be useful in determining body fat ratio. Insulin resistance markers are significantly higher in patients with cirrhosis, as disease severity advances resistin levels increases. We are in the opinion that resistin does not contribute to the development of insulin resistance, which occurs with different mechanisms in patients with cirrhosis.

Effects of luseogliflozin on the secretion of islet hormones and incretins in patients with type 2 diabetes.

The insufficient activity of insulin and the hyperactivity of glucagon are responsible for glucose intolerance in patients with type 2 diabetes. Whereas sodium-glucose cotransporter-2 (SGLT2) inhibitors improve blood glucose levels in patients with type 2 diabetes, their effects on the secretion profiles of glucagon and incretins remain unclear. Therefore, to investigate the effects of the SGLT2 inhibitor luseogliflozin on metabolic and endocrine profiles, 19 outpatients with type 2 diabetes were administered luseogliflozin for 12 weeks. It is of note that all subjects were treated only with diet and exercise therapy, and we were able to investigate the effects of luseogliflozin separately from the effects of other antidiabetic agents. Body weight, body fat mass, fat-free mass, and muscle mass were significantly reduced after 12 weeks of luseogliflozin administration. Glycosylated hemoglobin significantly decreased from the baseline of 8.2% ± 0.8% to 7.3% ± 0.7% (p < 0.0001). The meal tolerance test demonstrated that luseogliflozin significantly recovered glucose tolerance, accompanied by improved insulin resistance and β-cell function, whereas glucagon secretion was unaffected. Furthermore, GLP-1 secretion was significantly increased after luseogliflozin administration. Thus, luseogliflozin improved metabolic and endocrine profiles accompanied by increased GLP-1 secretion in type 2 diabetic patients without any antidiabetic medication, but did not affect glucagon secretion.

The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

BackgroundAdipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. Methods and ResultsProtein biomarkers (n = 276) from the Olink Proseek–Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (–14.8 mm Hg 95% confidence interval –18.45 to –11.12) compared with nonobese patients (–3.6 mm Hg 95% confidence interval –7.82 to 0.66). ConclusionsAmong patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

High frequency and long persistency of ballooning hepatocyte were associated with glucose intolerance in patients with severe obesity

Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance—demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test—and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.

STEROID-INDUCED GLUCOSE INTOLERANCE IN CHILDREN WITH NEPHROTIC SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOUS

Steroids are the cornerstone in treatment of idiopathic nephrotic syndrome (INS) and systemic lupus erythematosus (SLE). Steroids are used for their anti-inflammatory and immunosuppressive effects. Although, they are known to cause serious adverse effects including glucose intolerance.The mechanisms by which steroid-induced glucose intolerance (SIGI) include: increased gluconeogenesis in the liver, reduced glucose uptake in adipose tissue and skeletal muscle, and induced pancreatic β-cell dysfunction. The exact prevalence of SIGI in patients on chronic steroid therapy is unknown. The prevalence was reported to vary between 0% and 65% and several risk factors for the developing SIGI have been identified. THE AIM OF THIS WORK The aim of this work was to study steroid-induced glucose intolerance in patients with idiopathic nephrotic syndrome and systemic lupus erythematosus on long term steroid treatment and to determine the risk factors associated with development of steroid-induced glucose intolerance.SUBJECTSSubjects were recruited directly from outpatient Pediatric Nephrology Clinic. Sixty children aged from 2 to 18 years were enrolled; including 2 groups: thirty patients with INS and thirty patients with SLE on long-term steroids use for at least 6 months.

Pattern of Glucose Tolerance among Patients with Peripheral Spondyloarthritis

Peripheral spondyloarthritis is a variant of spondyloarthritis which usually has a chronic course. There is an increased risk of cardiovascular diseases among patients with chronic inflammatory diseases in general. Coexisting diabetes mellitus can potentially add to the risk. The objective of this study was to determine the frequency of glucose intolerance in patients with spondyloarthritis The study was conducted among 35 participants with peripheral spondyloarthritis who visited the Department of Rheumatology, Enam Medical College &amp; Hospital, Savar, Dhaka, Bangladesh from September, 2018 to January, 2020. The participants underwent either oral glucose tolerance test or estimation of HbA1C. The mean age of participants was 43.96 years. The majority (80%) of them were young to muddle-aged (≤40 years). 22.9% of the participants were prediabetic. Diabetes mellitus was found to be present in 37.1% of the participants. There was no significant difference between the study population and the general population in terms of frequency of prediabetes. But the frequency of diabetes in the study population was higher than that in the general population. There was no significant difference between males and females with regard to the frequencies of prediabetes and DM. Moreover, there was no significant difference in the frequencies of prediabetes and DM between young and middle-aged to elderly population. Considering the greater burden of DM among patients with peripheral spondyloarthritis across all age groups, routine screening for DM may be indicated in these individuals.

SUN-336 Obesity and Impaired Glucose Metabolism in Adult Patients with X-Linked Hypophosphatemia

Background: X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Epidemiologic studies suggest a relationship between FGF23, obesity and metabolic syndrome. However, the prevalence of metabolic complications in adult XLH patients is not known. Study design: We conducted a prospective cohort study (CNIL 2171036 v 0) in a single tertiary referral center. Subjects: Patients were adult subjects with XLH, defined as hypophosphatemia due to renal phosphate wasting with either documented PHEX mutation (92%) and/or family history of rickets. Healthy controls were selected among adult participants of the AcroCut cohort and matched for sex, age and body mass index (BMI). Methods: Prevalence of obesity and diabetes in patients was compared with the general French population (ObEpi 2012; Bonaldi C. et al., Bulletin épidemiologique hebdomadaire 2016) and prevalence of glucose intolerance in patients, assessed by standard 75-g OGTT, was compared to matched controls. Resistance to insulin was evaluated with HOMA-IR index. Results: 107 patients (79 women and 28 men) were recruited. Median age at evaluation was 35.5 years (range 16.9-74.2) and median BMI was 25 kg/m2 (range 18-48). Thirty-eight (35.5%) patients were overweight (29 women) and 22 (20.5%) patients were obese (16 women). Distribution of normal weight, overweight and obesity in adult XLH patients differed from that seen in the general French population. We observed an excess of overweight and obesity (+20%, 95% CI [+6; +33], P=0.013) in comparison to general population, especially in younger age categories (under 45 years of age). Three (2.8%) out of the 107 patients were treated for diabetes which did not differ from the expected frequency of type 2 diabetes of 5% in the French population. Twelve (13%) out of 90 patients with available OGTT were glucose intolerant or diabetic compared to ten (12%) of the 82 matched controls (P=0.995). Decreased insulin sensitivity assessed by HOMA-IR was found in fourteen (15.6%) adult XLH patients. Comparison of insulin and glucose curves obtained during the OGTT in patients and matched controls are planned to analyze insulin sensitivity in both populations. Conclusion: Adult XLH patients are prone to develop overweight and obesity, particularly adolescents and young adults. This excess of weight does not seem to result in increased prevalence of metabolic disorders. Insulin sensitivity, yet, needs to be further evaluated in these patients and compared to appropriate controls. FGF23 concentrations will also be assessed to search for determinants of insulin sensitivity in patients. Lifestyle recommendations to prevent obesity, promoting physical activity, are thus essential in the management of XLH patients.

Prediabetes &amp; Diabetes Among Patients with Axial Spondyloarthritis

Background & Objectives: There is an increased risk of cardiovascular diseases among patients with spondyloarthritis. Coexisting diabetes mellitus can potentially add to the risk. The objective of this study was to determine the frequency of glucose intolerance in patients with spondyloarthritis. Materials & Methods: The study was conducted among 85 participants with axial spondyloarthritis who visited the Department of Rheumatology, Enam Medical College & Hospital, Savar, Dhaka, Bangladesh from September, 2018 to December, 2019. The participants underwent either oral glucose tolerance test or estimation of HbA1C. Results: The mean age of participants was 40.6 years. The majority (57.6%) of them belonged to the young age group (18-40 years). 30.6% of the participants were prediabetic. Diabetes mellitus was found to be present in 20% of the participants. There was no significant difference between the study population and the general population in terms of frequency of prediabetes. But the frequency of diabetes in the study population was higher than that in the general population. There was no significant difference between males and females with regard to the frequencies of prediabetes and DM. Diabetes mellitus was more common in the elderly age group. Conclusion: Considering the greater burden of DM among patients with axial spondyloarthritis, routine screening for DM may be indicated in these individuals.

Glycated Albumin May Predict Early Postpartum Glucose Intolerance in Patients with Gestational Diabetes

Glycated Albumin May Predict Early Postpartum Glucose Intolerance in Patients with Gestational Diabetes

Differences in the actions of adrenaline and noradrenaline with regard to glucose intolerance in patients with pheochromocytoma

Glucose intolerance is often observed in patients with pheochromocytoma. However, it remains controversial issue that glucose intolerance on pheochromocytoma is caused by impaired insulin secretion and/or by increased insulin resistance. We aimed to reveal the mechanism of glucose intolerance on pheochromocytoma with regard to the type and amount of catecholamines released. We evaluated 12 individuals diagnosed with pheochromocytoma and who underwent surgery to remove it. We examined glycemic parameters before and after surgery and investigated the association between the change of parameters of insulin secretion (homeostasis model assessment of β-cell function (HOMA-β)), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) and that of urinary levels of metanephrine/normetanephrine before and after surgery. Overall, fasting plasma glucose, glycated hemoglobin (HbA1c), HOMA-β, and HOMA-IR were improved significantly after surgery. Regression analysis showed that the improvement in HOMA-β from before to after surgery was significantly positively associated with an improvement in urinary levels of metanephrine from before to after surgery and showed a significantly negative association with improvement in urinary levels of normetanephrine from before to after surgery. The improvement in HOMA-IR from before to after surgery was significantly positively associated with an improvement in urinary levels of normetanephrine from before to after surgery. Our results showed that pheochromocytoma extirpation improved glycemic parameters. Furthermore, the different effects elicited by excess amounts of adrenaline and noradrenaline on glucose intolerance were demonstrated.

Glucose metabolism before and after radioiodine therapy of a patient with Graves' disease: Assessment by continuous glucose monitoring.

Hyperthyroidism causes impaired glucose tolerance, insulin resistance (IR) and insulin secretion. However, the glucose variability affected by thyroid dysfunction remains unclear. Glucose variability was assessed by continuous glucose monitoring (CGM) in a non-diabetic patient with Graves' disease (GD), to the best of our knowledge, for the first time. A 28-year-old man with GD, who had been taking methimazole for 4 years, was treated with radioiodine on August 17th 2016. Although the patient exhibited normal glycated hemoglobin (HbA1c; 5.3%) and blood glucose values during the oral glucose tolerance test (OGTT; fasting and 120 min blood glucose were 5.38 and 6.39 mmol/l, respectively) before radioiodine therapy, CGM exhibited high 24 h mean glucose and nocturnal hyperglycemia. An increased fasting insulin level, suppressed levels of blood glucagon and high homeostatic model assessment of IR were also observed. The disordered glucose metabolism improved as soon as the patient's thyroid function turned to hypothyroidism 4 months after radioiodine therapy. The glucose intolerance in patients with hyperthyroidism, missed by the OGTT and HbA1c tests, may be more common than anticipated.

Variation of glucose tolerance in adult patients with cystic fibrosis: What is the potential contribution of insulin sensitivity?

BackgroundReduced insulin secretion is a key factor to explain high prevalence of glucose intolerance in patients with cystic fibrosis (CF). However, the role of insulin sensitivity remains unclear. The aim of this study is to investigate the association of insulin secretion and sensitivity with the evolution of glucose tolerance. MethodsA total of 152 patients without known diabetes from the Montreal CF cohort underwent two 2-h oral glucose tolerance tests (OGTT) at baseline and again after 21.2±5.5months. Pulmonary function and anthropometric measurements were also collected at each visit. At both visits, based on their OGTT results, patients were categorized in glucose tolerance groups (normal glucose tolerance, impaired glucose tolerance or CF-related diabetes) and stratified in 3 groups according to the variation of their glucose tolerance: stable, improved or deteriorated. ResultsAt baseline, patients in the deteriorated group had a better sensitivity to insulin than those in the improved group (P=0.029). At follow-up glucose tolerance remained stable in 55.3%, improved in 14.5% and deteriorated in 30.3% of patients. During follow-up, insulin secretion remained stable in all 3 groups. While insulin sensitivity remained stable in patients without changes in glucose tolerance it worsened in patients who deteriorated glucose tolerance (P<0.001) and improved in patients who improved their glucose tolerance (P=0.003). ConclusionIn a context of significantly reduced insulin secretion, variations of insulin sensitivity are associated with variations of glucose tolerance in adult patients with CF.

Case of aniridia with a heterozygous PAX6 mutation in which the glucagon response to arginine was evaluated.

Pax6 is a highly evolutionally conserved transcription factor involved in the development of the eye and pancreatic islets. In humans, a heterozygous PAX6 mutation causes aniridia and mild glucose intolerance with impaired insulin secretion1. However, there have been no reports evaluating pancreatic α-cell function in aniridia patients with heterozygous PAX6 mutations. We herein present the first case of an aniridia patient with a heterozygous PAX6 mutation in which pancreatic α-cell function was evaluated. A 40-year-old woman with aniridia and obesity (165 cm, 86 kg, body mass index 31.6 kg/m2) was admitted to the Department of Metabolic Medicine, Osaka Hospital, Suita, Japan, for an endocrine examination. In childhood, she was diagnosed with aniridia, and at 28 years-of-age, it was found that she had a heterozygous PAX6 mutation (c.969C>T) leading to a truncated protein lacking a transactivation domain. The mutant PAX6 protein in the patient did not exert any transcriptional activity1. On admission, a 75-g oral glucose tolerance test showed impaired glucose tolerance (IGT) with impaired insulin secretion (Table​(Table1).1). On an arginine stimulation test (a 10% L-arginine hydrochloride solution [300 mL] was given intravenously over 30 min), the area under the concentration–time curve for the immunoreactive glucagon (AUCIRG) between time 0 and 120 min was calculated by means of the trapezoidal rule. The serum glucagon concentration was measured by RIA (SRL, Tokyo, Japan) similar to that in non-diabetic Japanese controls2. As a result, AUCIRG in the present case was comparable with that in non-diabetic Japanese controls (25.9 pg/mL/min × 103 vs 25.20 ± 7.76 pg/mL/min × 103)2. Table 1 Results of 75-g oral glucose tolerance test in the patient Recently, the involvement of glucagon in the pathogenesis of diabetes has drawn much attention. Pax6 is a transcription factor involved in the development of pancreatic α- and β-cells. Mice with a targeted disruption of Pax6 die soon after birth with an absence of glucagon-producing α-cells and a marked reduction of insulin producing β-cells. In heterozygous Pax6 mutant mice lacking a transactivation domain similar to the present case, α- and β-cells are reduced to 25 and 40% of wild type3. In contrast, aniridia patients with heterozygous PAX6 mutations had mild glucose intolerance with impaired insulin secretion1. However, secretory properties of glucagon in those patients were unclear. The present case showed impaired insulin secretion, whereas her glucagon response to arginine was comparable with those in non-diabetic control subjects. Although we could not conclude, because we failed to assess the glucagon responses to arginine in the control subjects with obese and IGT, and the other subjects with PAX6 mutation, this result might not necessarily show that her glucagon capacity is normal. This is because it has been shown that glucagon response to arginine in patients with IGT and/or obesity, as well as the present case, is exaggerated. Therefore, the result that her glucagon secretory capacity was not exaggerated despite her obesity and IGT could suggest her impaired glucagon secretory capacity. To the best of our knowledge, the present case is the first report to evaluate pancreatic α-cell function in a patient with a heterozygous PAX6 mutation. In addition, interestingly, recent studies have shown that blocking glucagon action prevents diabetes4. Considering these results, the cause of a mild degree of glucose intolerance in patients with heterozygous PAX6 mutations might be partially because of decreased glucagon secretion. In conclusion, we presented the first case of an aniridia patient with a heterozygous PAX6 mutation in which the glucagon response to arginine was evaluated. Further human studies are required to show the association of PAX6 mutations with glucagon secretion.

Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study.

BackgroundGlucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan.MethodsThe study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease.ResultsOver a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10–1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13–1.94) than in women (HR 1.17; 95% CI, 0.84–1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18–2.36).ConclusionsThis study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.

Investigation of glucose intolerance in patients with normocalcemic primary hyperparathyroidism: 4-year follow-up

Normocalcemic primary hyperparathyroidism (NPHPT) is a clinical phenomenon in which elevated serum PTH levels are observed with normal serum calcium concentrations in lack of secondary causes such as vitamin D deficiency, renal or liver disease or malabsorption [1, 2]. While derangements in glucose and lipid metabolism in primary hyperparathyroid patients are well-defined, only a few reports exist regarding metabolic abnormalities in patients with NPHPT. Recently, we have shown in 18 patients with NPHPT that those patients do not exhibit increased rates of insulin resistance and glucose intolerance [3]. Similarly, Tassone et al. [4] also showed that patients with NPHPT have similar insulin sensitivity and glucose tolerance with age and sexmatched control subjects. Since there is no prospective study in patients with NPHPT, we have evaluated the changes regarding insulin resistance and glucose intolerance in the same patient group after 4 years of follow-up. Sixteen patients (2 males and 14 females) out of 18 with NPHPT were admitted to regular visits during the 4 years after their first diagnosis as NPHPT. Two patients did not come to visits. The whole data of the patients were described previously [3]. All subjects underwent a physical examination and biochemical data including serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, serum lipids, 25 (OH) D levels were determined regularly after an overnight fast. Standart oral glucose tolerance test (OGTT) with 75 g glucose were started between 08:00 and 09:00 h. Blood samples were taken just before (0 min) and 30, 60, 90 and 120 min after administration of glucose with 300 ml water orally for the measurement of serum glucose and insulin concentrations. Area under the curves (AUC) of glucose and insulin during OGTT were calculated according to trapezoid rule. Glucose tolerance was evaluated by using the criteria of the American Diabetes Association, and impaired glucose tolerance (IGT) was defined as a 2-h post-load glucose of C140 and \200 mg/dl. Statistical analysis was performed using the SPSS 15.0 program. All data were subjected to a Kolmogorov–Smirnov test for normality and data was presented as mean ± SEM. Paired t test was used to compare differences at the beginning and at the end of the study. P \ 0.05 was accepted as significancy. Four years of data after initial diagnosis for each patient were evaluated. One (6.25 %) patient developed hypercalcemic hyperparathyroidism. The data of this patient was not used in the analysis. Serum PTH level was significantly higher (103.8 ± 12.5 pg/ml) than normal limits (5–65 pg/ml) at the end of the 4 years. None of the patients had vitamin D deficiency [mean serum 25 (OH) D level was 54.6 ± 5.9 ng/ml]. Three out of five patients with IGT had diabetes mellitus and the two others remained as IGT at the end of the 4 years. None of the patients with normal glucose tolerance developed glucose intolerance during follow-up. The patient who developed hypercalcemia and three patients with diabetes mellitus were excluded from the analysis and we found that insulin responses to OGTT were not significantly different before (AUCinsulin 5059 ± 765 mg/dl 9 120 min) and after 4 years (AUCinsulin 4293 ± 537 mg/dl 9 120 min) of follow-up. Serum lipid levels, kidney and liver function tests were also normal during 4 years follow-up. Several previous data demonstrated close relationship between primary hyperparathroidism (PHPT) and impaired H. Diri K. Unluhizarci (&) F. Kelestimur Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey e-mail: kursad@erciyes.edu.tr

Clinical significance of glycated hemoglobin in the acute phase of ST elevation myocardial infarction.

In population-based studies, including diabetic and nondiabetic cohorts, glycated hemoglobin A1c (HbA1c) has been reported as an independent predictor of all-cause and cardiovascular disease mortality. Data on the prognostic role of HbA1c in patients with acute myocardial infarction (MI) are not univocal since they stem from studies which mainly differ in patients' selection criteria, therapy (thrombolysis vs mechanical revascularization) and number consistency. The present review is focused on available evidence on the prognostic significance of HbA1c measured in the acute phase in patients with ST-elevation myocardial infarction (STEMI) submitted to primary percutaneous coronary intervention (PCI). We furthermore highlighted the role of HbA1c as a screening tool for glucose intolerance in patients with STEMI. According to available evidence, in contemporary cohorts of STEMI patients submitted to mechanical revascularization, HbA1c does not seem to be associated with short and long term mortality rates. However, HbA1c may represent a screening tool for glucose intolerance from the early phase on in STEMI patients. On a pragmatic ground, an HbA1c test has several advantages over fasting plasma glucose or an oral glucose tolerance test in an acute setting. The test can be performed in the non-fasting state and reflects average glucose concentration over the preceding 2-3 mo. We therefore proposed an algorithm based on pragmatic grounds which could be applied in STEMI patients without known diabetes in order to detect glucose intolerance abnormalities from the early phase. The main advantage of this algorithm is that it may help in tailoring the follow-up program, by helping in identifying patients at risk for the development of glucose intolerance after MI. Further validation of this algorithm in prospective studies may be required in the contemporary STEMI population to resolve some of these uncertainties around HbA1c screening cutoff points.