Metabolic dysfunction-associated steatotic liver disease is associated with worse time in ranges in type 1 diabetes.

AIM: To investigate the relationship between continuous glucose monitoring (CGM)-derived glucometrics and metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes (T1D). METHODS: A cross-sectional study collecting data on anthropometrics, glucometrics and MASLD in adults with T1D using a CGM device was conducted. MASLD was assessed by abdominal ultrasound and the presence of at least one cardiometabolic criterion. Backward multivariable logistic regression models were applied to define variables independently associated with MASLD. RESULTS: A total of 302 consecutive participants were included (median age 49 [34-61] years, male sex 58%, median diabetes duration 29 [17-38] years, mean time in range [TIR] 55% ± 16%). MASLD was present in 17% of cases, and 32% had metabolic syndrome (MetS). MetS was significantly more prevalent in the MASLD group (65% vs. 25%, P < .0001). TIR (P = .038) and time below range (TBR) (P = .032) were lower and time above range (TAR) was higher (P = .006), whereas HbA1c did not reach significance (P = .068). No differences were found for the glycaemia risk index. TIR (P = .028), TAR (P = .007), TBR (P = .036), waist circumference (P < .001) and systolic blood pressure (P = .029) were independently associated with MASLD, while sex, age, aspartate aminotransferase/alanine aminotransferase ratio, gamma-glutamyl transferase, high-density lipoprotein cholesterol and triglycerides were not. CONCLUSIONS: TIR, TAR, TBR, waist circumference and systolic blood pressure were independently associated with MASLD.

Rapid-acting insulin analogues: Theory and best clinical practice in type 1 and type 2 diabetes.

Since the discovery of insulin 100 years ago, insulin preparations have improved significantly. Starting from purified animal insulins, evolving to human insulins produced by genetically modified organisms, and ultimately to insulin analogues, all in an attempt to mimic physiological insulin action profiles seen in individuals without diabetes. Achieving strict glucose control without hypoglycaemia and preventing chronic complications of diabetes while preserving quality of life remains a challenging goal, but the advent of newer ultra-rapid-acting insulin analogues may enable intensive insulin therapy without being too disruptive to daily life. Ultra-rapid-acting insulin analogues can be administered shortly before meals and give better coverage of mealtime-induced glucose excursions than conventional insulin preparations. They also increase convenience with timing of bolus dosing. In this review, we focus on the progress that has been made in rapid-acting insulins. We summarize pharmacokinetic and pharmacodynamic data, clinical trial data supporting the use of these new formulations as part of a basal-bolus regimen and continuous subcutaneous insulin infusion, and provide a clinical perspective to help guide healthcare professionals when and for whom to use ultra-fast-acting insulins.

Efficacy and safety of high-dose glucagon-like peptide-1, glucagon-like peptide-1/glucose-dependent insulinotropic peptide, and glucagon-like peptide-1/glucagon receptor agonists in type 2 diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high-risk individuals. With currently available GLP-1 RAs, 51%-79% of subjects achieve an HbA1c target of less than 7.0% and 4%-27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms 'glucagon-like peptide-1 receptor agonist', 'glucagon receptor agonist', 'glucose-dependent insulinotropic peptide', 'dual or co-agonist', and 'tirzepatide'. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high-dose GLP-1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high-dose GLP-1 RAs or tirzepatide, respectively. The glucose- and weight-lowering effects of the GLP-1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high-dose GLP-1 RAs and co-agonists occurred in 30%-70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high-dose GLP-1 RAs and the dual GLP-1/glucose-dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15-mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied.

Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes.

Background & Aims: The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods: In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results: Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. Conclusions: NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and Implications: We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.

Microbiome-derived ethanol in nonalcoholic fatty liver disease.

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10-5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.

Autoimmune gastritis in type 1 diabetes: a clinically oriented review.

CONTEXT: Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS: Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION: The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus.

Context: Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases. Evidence Acquisition: Systematic search of four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) using the search terms "diabetes" or "ketoacidosis" and "pembrolizumab," "nivolumab," "PD-1 inhibitor," or "immunotherapy." Included were articles published in English between 1 January 2012 and 1 January 2018. The search was supplemented by bibliographic searches of the complete reference lists of all included papers. Evidence Synthesis: We provide an overview of all published cases (n = 42) of PD-1 inhibitor-induced type 1 diabetes mellitus to date, including a well-characterized case of islet cell antibody and glutamic acid decarboxylase antibody-positive diabetes mellitus, in a patient with a diabetes-prone HLA genotype. She presented with diabetic ketoacidosis during pembrolizumab therapy for a metastatic uveal melanoma. Furthermore, we discuss potential pathogenic mechanisms, clinical presentation, prognostic markers (ß-cell antibodies and HLA type), treatment, and a screening protocol. Conclusions: Because the use of immunotherapy will increase, it is essential that all clinicians are aware of diabetic ketoacidosis as a rare and life-threatening side effect of immunotherapy. Blood glucose monitoring during anti-PD-1 therapy is necessary.

Predicting type 2 diabetes mellitus: a comparison between the FINDRISC score and the metabolic syndrome.

BACKGROUND: The aim of this study to compare the diagnostic accuracy of the metabolic syndrome (MetS) with the FINDRISC score to screen for type 2 diabetes mellitus T2DM in an overweight/obese population. METHODS: Subjects 18 years or older visiting the obesity clinic of the Antwerp University Hospital were consecutively recruited between 2012 and 2014. Every patient underwent a standard metabolic work-up including a clinical examination with anthropometry. Glucose status was tested using OGTT and Hba1c. FINDRISC questionnaire and MetS were examined. RESULTS: Of 651 subjects, 50.4% were diagnosed with prediabetes, whereas 11.1% was diagnosed with T2DM. FINDRISC score increased with worsening of glucose status 11 ± 3, 13 ± 4 and 15 ± 5 in respectively, subjects without T2DM, prediabetes and T2DM. 312 subjects had the MetS. The aROC of the FINDRISC to identify subjects with T2DM was 0.76 (95% CI 0.72-0.82), sensitivity was 64% and specificity was 63% with 13 as cutoff point. Adding FPG or HbA1c to FINDRISC, the aROC increased significantly to 0.91(95% CI 0.88-0.95) and 0.93(95% CI 0.90-0.97), respectively (p < 0.001). The aROC of the MetS to identify subjects with diabetes was 0.72 (95% CI 0.65-0.78), sensitivity was 75% and specificity was 55%. The aROC of the FINDRISC + HbA1c was significantly higher than the MetS for predicting T2DM (p < 0.001). CONCLUSION: Prediction of type 2 diabetes is important for timely intervention and to avoid chronic complications associated with the disease. Our findings suggest, that it may be of good clinical practice to use the FINDRISC score + HbA1c in a two-step screening model for diabetes rather than using the metabolic syndrome.

Coronary artery calcifications and diastolic dysfunction versus visceral fat area in type 1 diabetes: VISCERA study.

AIMS: Type 1 diabetic patients (T1DM) experience a higher cardiovascular disease and mortality risk than controls. We investigated whether visceral adipose tissue (VAT) contributes to coronary artery calcifications (CAC) and cardiac dysfunction in T1DM. METHODS: A cross-sectional study of 118 T1DM patients without a history of cardiovascular disease (men/women: 68/50, age 46±12years, HbA1c 7.6±0.9%, BMI 25.8±4.1kg/m2) was conducted. CAC and VAT were measured using a CT scan. CAC was scored using the Agatston method. Cardiac functional abnormalities were assessed by echocardiography. RESULTS: CAC scored ≥10 in 42% of patients. Systolic function was normal in all, but diastolic dysfunction was present in 75%. Forty-six percent had VAT≥100cm2. CAC score≥10 occurred more often in subjects with VAT≥100cm2 (54% vs 31%; p=0.01). Age (OR=1.10; p<0.0001), diabetes duration (OR=1.10; p=0.008), gender (OR=4.28; p=0.016), LDL-cholesterol (OR=1.03; p=0.009) and metabolic syndrome (OR=5.79; p=0.005) were independently associated with a CACS≥10. Subjects with CACS≥10 were more prone to have diastolic dysfunction (84 vs 54%; p=0.03). Factors independently associated with diastolic dysfunction were age (OR=1.11; p=0.002), waist circumference (OR=1.10; p=0.016) and VAT (OR=0.99; p=0.035). CONCLUSIONS: Excess VAT in T1DM, present in 46%, is associated with diastolic dysfunction and CAC, present in respectively 75% and 42% of patients. Timely detection might improve future cardiovascular risk.

Impact of overweight on chronic microvascular complications in type 1 diabetic patients.

OBJECTIVE: To investigate a possible association of BMI with retinopathy and neuropathy in type 1 diabetes. Retinopathy and neuropathy may not only be related to glycemic control and diabetes duration but also to blood pressure and BMI. RESEARCH DESIGN AND METHODS: A total of 592 type 1 diabetic patients without nephropathy were studied (M/F: 324/268; age: 41 +/- 12 years; duration: 19 +/- 11 years; HbA(1c) [A1C]: 7.9 +/- 1.1%). Patients were subdivided according to BMI: 168 men and 146 women with BMI <25 kg/m(2), and 156 men and 122 women with BMI > or =25 kg/m(2). Retinopathy was examined by fundoscopy and neuropathy by electromyography. RESULTS: Hypertension (>130/85 mmHg) was present in 40%, retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had more retinopathy (63 vs. 45%, P < 0.0001, odds ratio [OR] = 2.1) and neuropathy (49 vs. 38%, P = 0.008, OR = 1.6) than normal-weight patients. Patients with retinopathy were older (45 +/- 12 vs. 37 +/- 11 years, P < 0.0001) and had a longer diabetes duration (25 +/- 10 vs. 12 +/- 8 years, P < 0.0001), a higher A1C (8.0 +/- 1.1 vs. 7.7 +/- 1.1%, P = 0.001), and a higher BMI (25.8 +/- 4.1 vs. 24.7 +/- 4.2 kg/m(2), P = 0.001) than individuals without retinopathy. The same results are found in neuropathy. Logistic regression analysis showed that diabetes duration (beta = 0.15, P < 0.0001), blood pressure (beta = 0.22, P = 0.0047), and A1C (beta = 0.24, P = 0.01), but not BMI, lipid levels, sex, or age, were independent risk factors for retinopathy. Likewise, duration (beta = 0.05, P < 0.0001), age (beta = 0.04, P = 0.0001), A1C (beta = 0.35, P < 0.0001), and sex (beta = 0.74, P = 0.0001) but not BMI, lipid levels, or hypertension were independently associated with neuropathy. Men had more neuropathy than women (50 vs. 34%, P < 0.0001, OR = 1.9). Leptin and adiponectin levels did not differ between individuals with or without microvascular complications. CONCLUSIONS: Retinopathy and neuropathy are more prevalent in overweight (BMI > or =25 kg/m(2)) type 1 diabetic subjects. However, logistic regression analysis showed that diabetes duration and A1C remain the main determinants for retinopathy and neuropathy.

A comparison of two insulin infusion protocols in the medical intensive care unit by continuous glucose monitoring.

BACKGROUND: Achieving good glycemic control in intensive care units (ICU) requires a safe and efficient insulin infusion protocol (IIP). We aimed to compare the clinical performance of two IIPs (Leuven versus modified Yale protocol) in patients admitted to medical ICU, by using continuous glucose monitoring (CGM). This is a pooled data analysis of two published prospective randomized controlled trials. CGM monitoring was performed in 57 MICU patients (age 64 ± 12 years, APACHE-II score 28 ± 7, non-diabetic/diabetic: 36/21). The main outcome measures were percentage of time in normoglycemia (80-110 mg/dl) and in hypoglycemia (<60 mg/dl), and glycemic variability (standard deviation, coefficient of variation, mean amplitude of glucose excursions, mean of daily differences). RESULTS: Twenty-two subjects were treated using the Leuven protocol and 35 by the Yale protocol; >63,000 CGM measurements were available. The percentage of time in normoglycemia (80-110 mg/dl) was higher (37 ± 15 vs. 26 ± 11%, p = 0.001) and percentage of time spent in hypoglycemia was lower (0[0-2] vs. 5[1-8]%, p = 0.001) in the Yale group. Median glycemia did not differ between groups (118[108-128] vs. 128[106-154] mg/dl). Glycemic variability was less pronounced in the Yale group (median SD 28[21-37] vs. 47[31-71] mg/dl, p = 0.001; CV 23[19-31] vs. 36[26-50]%, p = 0.001; MODD 35[26-41] vs. 60[33-94] mg/dl, p = 0.001). However, logistic regression could not identify type of IIP, diabetes status, age, BMI, or APACHE-II score as independent parameters for strict glucose control. CONCLUSIONS: The Yale protocol provided better average glycemia, more time spent in normoglycemia, less time in hypoglycemia, and less glycemic variability than the Leuven protocol, but was not independently associated with strict glycemic control.

Delayed gastric emptying and gastric autoimmunity in type 1 diabetes.

OBJECTIVE: Delayed gastric emptying and/or gastrointestinal symptoms occur in 30-50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA(1c), thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology. RESEARCH DESIGN AND METHODS: Gastric emptying of solids and liquids (measured by (13)C-octanoic acid and (13)C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 +/- 15 years; mean HbA(1c) 7.8 +/- 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed. RESULTS: Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA(1c) level (beta = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA(1c), autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = -0.79, P = 0.001). CONCLUSIONS: We found that approximately 50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.

Autoimmune gastropathy in type 1 diabetic patients with parietal cell antibodies: histological and clinical findings.

OBJECTIVE: Approximately 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients. RESEARCH DESIGN AND METHODS: Gastric biopsies from 88 consecutively recruited type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 +/- 13 years) were evaluated using the updated Sydney system. Immunostaining was done for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence, H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath test, and histology. Pentagastrin tests were performed in 42 subjects. RESULTS: Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P < 0.0001). PCA positivity (beta = 1.44; P = 0.04) and hypergastrinemia (beta = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015), pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P = 0.0002) were more frequent in AG+ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG+ patients, including 1 with linitis plastica. CONCLUSIONS: PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.

Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes.

OBJECTIVE: Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia. RESEARCH DESIGN AND METHODS: Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies. RESULTS: PCA(+) patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(-) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor. CONCLUSIONS: PCA(+) patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.

Randomized Evaluation of Glycemic Control in the Medical Intensive Care Unit Using Real-Time Continuous Glucose Monitoring (REGIMEN Trial).

BACKGROUND AND OBJECTIVE: Hyperglycemia occurs commonly in patients admitted to medical intensive care units (MICUs). Whether real-time (RT) continuous glucose monitoring (CGM) improves glycemic control and variability and reduces hypoglycemia in severely ill MICU patients with an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score of ≥20 has not been studied. SUBJECTS AND METHODS: Thirty-five patients (66 ± 10 years of age; APACHE-II score, 28 ± 6) were randomly assigned to RT-CGM (n = 16) using the GlucoDay(®)S (A. Menarini Diagnostics, Florence, Italy) device or to blinded CGM. Insulin was infused using a modified Yale protocol targeting a blood glucose level between 80 and 120 mg/dL. Outcome measures were percentage of time in normoglycemia (80-110 mg/dL) and in hypoglycemia (<60 mg/dL), glycemic variability (SD, coefficient of variation, mean amplitude of glucose excursions, and mean of daily differences), and CGM accuracy (error grid analyses, Bland-Altman bias plot, and mean absolute relative deviation). RESULTS: During 96 h of monitoring, glycemia reached target (80-110 mg/dL) in 37 ± 15%, was between 70 and 180 mg/dL in 91 ± 10%, and <60 mg/dL in 2 ± 2% of the time. In the RT-CGM group glycemia averaged 119 ± 17 mg/dL versus 122 ± 11 mg/dL in the control group. Parameters of glucose variability and percentages of time at target glycemia and in hypoglycemia were similar between groups. GlucoDayS values and arterial glycemia correlated well, with 98.6% of data falling in Zones A and B of the error grid analysis. Mean absolute relative devation was 11.2%. CONCLUSIONS: RT-CGM did not ameliorate glucose control or variability; neither did it reduce the number of hypoglycemic events, but our insulin infusion protocol led to overall good glucose control without a significant hypoglycemia risk, making further improvement difficult.

Bariatric surgery to treat type 2 diabetes: what is the recent evidence?

PURPOSE OF REVIEW: To critically discuss the strengths and shortcomings of recent progress achieved with bariatric surgery in patients with type 2 diabetes mellitus (T2DM), focussing on efficacy aspects (remission of diabetes and cardiovascular comorbidities). Despite an increasing armamentarium of pharmacotherapeutics to overcome several challenges, only 10% of T2DM patients achieve a composite goal of HbA1c, blood pressure and lipids. Bariatric surgery has emerged as a solution to these challenges in morbid obesity. Whether the same advantages can be translated into T2DM remains a matter of debate, certainly regarding safety, durability of diabetes recovery and long-term outcome. RECENT FINDINGS: Bariatric surgery in T2DM patients with a BMI of at least 35 kg/m(2) has been shown to result in a 56% excess body weight loss, resolution of hypertension in 62%, amelioration of dyslipidaemia in greater than 70% and diabetes remission in 57-95%, depending on the type of surgery and the definition of diabetes resolution. These impressive results, and the fact that diabetes recovery often occurs before prominent weight loss is evident, have urged bariatric surgeons to consider surgical procedures as a valuable approach for diabetes control and diabetes remission in patients with a BMI ranging between 30 and 35 kg/m(2). SUMMARY: Bariatric surgery is emerging as a valid option to treat T2DM, improving glycaemia and cardiovascular risk factors. However, there needs to be an agreed definition of resolution of diabetes in future studies and long-term efficacy is to be proven. For now, the challenge is to determine how to offer bariatric surgery in a responsible fashion.

Current concepts in gastric motility in diabetes mellitus.

This review addresses the current concepts in our understanding of the epidemiology, mechanisms, symptoms, clinical consequences, diagnosis and treatment of delayed gastric emptying in patients with diabetes. Upper gastrointestinal symptoms, particularly postprandial fullness, nausea, vomiting and abdominal bloating, occur in 30-50% of patients with diabetes. The use of scintigraphic techniques, and more recently breath test, has shown that as many as 50% of diabetic patients have gastroparesis. Diabetic gastroparesis comprises a decrease in fundic and antral motor activity, a reduction or a lack of the interdigestive migrating motor complex, gastric dysrhythmias, and pylorospasms. The mechanisms involved include: autonomic neuropathy, acute hyperglycaemia, and abnormalities in gastrointestinal hormones and neuropeptides. Other possible contributing factors such as hypothyroidism and H. pylori infection are discussed as well. Because treatment is possible by means of dietary advise, prokinetics or surgical procedures, it is important to identify risk factors for and to diagnose gastroparesis to prevent morbidity by controlling gastrointestinal symptoms, and to enhance glucoregulation. Understanding the current advances is key to the development of novel therapeutic strategies and for making rational choices in the management of diabetic gastroparesis.