Diagnosis of hepatocellular adenoma in men before onset of diabetes in HNF1A-MODY: Watch out for winkers.

Hepatocyte nuclear factor 1A (HNF1A) maturity-onset diabetes of the young (MODY) is a monogenetic, autosomal dominantly inherited form of diabetes. HNF1A-MODY is associated with HNF1A-inactivated hepatocellular adenoma (H-HCA) formation. Hepatocellular adenoma (HCA) are benign liver tumours and related complications are rare but serious: hepatic haemorrhage and malignant transformation. Guidelines recommend resection of all HCA in men and do not take any co-occurring metabolic disorders into account. We report a family with HCA preceding diabetes mellitus. Male index patient presented with numerous, irresectable HCA. After initial diagnostic and aetiologic uncertainty HNF1A germline mutation c.815G>A (p.Arg272His) was confirmed 8 years later. No HCA-related complications occurred. His diabetic mother was diagnosed with HCA after severe hepatic haemorrhage years before. HNF1A-MODY should be considered in (non-)diabetic (male) patients with H-HCA. We advocate liver biopsy and, if necessary, genetic analysis to precede any intervention for HCA in males and screening for HCA in HNF1A-MODY patients.

Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease.

The aim of the present study was to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in patients with prednisone-induced hyperglycaemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicentre double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared with placebo. Glycaemic control and incidence of hypoglycaemia were measured through a blinded subcutaneous continuous glucose monitoring device. Participants in the dapagliflozin group spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and participants in the placebo group spent 53.6 ± 23.4% of the time in target range (P = .96). The mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (P = .66). One participant using dapagliflozin and 2 participants using placebo experienced symptomatic hypoglycaemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycaemia compared with placebo. Dapagliflozin did not result in better glycaemic control compared with placebo in participants with prednisone-induced hyperglycaemia during AECOPD.

Incidence and determinants of hypophosphatemia in diabetic ketoacidosis: an observational study.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia in DKA often occurs during hospital admittance for DKA. Literature on the magnitude, determinants and consequences of hypophosphatemia in DKA is scarce. Primary aim of this study was to investigate the incidence and consequences of hypophosphatemia during hospitalisation for DKA. RESEARCH DESIGN AND METHODS: Cohort study among individuals with T1DM who were admitted for DKA between 2005 and 2020 in an academic and a non-academic hospital. Multivariate regression models were performed to investigate determinants of the lowest phosphate during the treatment of DKA. RESULTS: A total of 127 episodes of DKA among 80 individuals were identified. Age at DKA presentation was 28 (22-46) years, 45% of the cases was female, diabetes duration was 13.2 (8.9-25.5) years with glycosylated hemoglobin levels of 91.9±26.2 mmol/mol. In 9% of all cases, DKA was the first presentation of T1DM. Lowest phosphate levelss reported during the treatment phase were 0.54 (0.32-0.83) mmol/L and hypophosphatemia was present in 74% (62/84). The time to lowest phosphate was 16 (8-23) hours. In multivariate analysis, baseline bicarbonate and hemoglobin at admission were significantly associated with the lowest phosphate level reported. No adverse effects of hypophosphatemia on hospital stay duration, morbidity or mortality were found, even if left untreated. CONCLUSIONS: Hypophosphatemia during DKA is common and increases with severe acidosis. However, in this study it was not related to adverse outcomes. Although limitations of this retrospective study should be taken into account, the routine and repeated measurement of phosphate levels in DKA could be reconsidered, provided that possible symptoms related to hypophosphatemia are monitored.

Glucose variability is associated with intensive care unit mortality.

OBJECTIVE: Mounting evidence suggests a role for glucose variability in predicting intensive care unit (ICU) mortality. We investigated the association between glucose variability and intensive care unit and in-hospital deaths across several ranges of mean glucose. DESIGN: Retrospective cohort study. SETTING: An 18-bed medical/surgical ICU in a teaching hospital. PATIENTS: All patients admitted to the ICU from January 2004 through December 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two measures of variability, mean absolute glucose change per hour and sd, were calculated as measures of glucose variability from 5728 patients and were related to ICU and in-hospital death using logistic regression analysis. Mortality rates and adjusted odds ratios for ICU death per mean absolute glucose change per hour quartile across quartiles of mean glucose were calculated. Patients were treated with a computerized insulin algorithm (target glucose 72-126 mg/dL). Mean age was 65 +/- 13 yrs, 34% were female, and 6.3% of patients died in the ICU. The odds ratios for ICU death were higher for quartiles of mean absolute glucose change per hour compared with quartiles of mean glucose or sd. The highest odds ratio for ICU death was found in patients with the highest mean absolute glucose change per hour in the upper glucose quartile: odds ratio 12.4 (95% confidence interval, 3.2-47.9; p < .001). Mortality rates were lowest in the lowest mean absolute glucose change per hour quartiles. CONCLUSIONS: High glucose variability is firmly associated with ICU and in-hospital death. High glucose variability combined with high mean glucose values is associated with highest ICU mortality. In patients treated with strict glycemic control, low glucose variability seemed protective, even when mean glucose levels remained elevated.

Hypoglycemia is associated with intensive care unit mortality.

OBJECTIVE: The implementation of intensive insulin therapy in the intensive care unit is accompanied by an increase in hypoglycemia. We studied the relation between hypoglycemia on intensive care unit mortality, because the evidence on this subject is conflicting. DESIGN: Retrospective database cohort study. SETTING: An 18-bed medical/surgical intensive care unit in a teaching hospital (Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, The Netherlands). PATIENTS: A total of 5961 patients admitted to from 2004 to 2007 were analyzed. Readmissions and patients with a withholding care policy or with hypoglycemia on the first glucose measurement were excluded. Patients were treated with a computerized insulin algorithm (target glucose range, 72-126 mg/dL). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All first episodes of hypoglycemia (glucose < or =45 mg/dL) were derived from 154,015 glucose values. Using Poisson regression, the incidence rates for intensive care unit death and incidence rate ratio comparing exposure and nonexposure to hypoglycemia were calculated. Patients were considered to be exposed to hypoglycemia from the event until the end of intensive care unit admittance. We corrected for severity of disease using the daily Sequential Organ Failure Assessment score. Age, sex, cardiothoracic surgery, sepsis, and diabetes mellitus were also included as possible confounders. Two hundred eighty-eight (4.8%) patients experienced at least one episode of hypoglycemia. Median age was 68 yrs (range, 58-75 yrs), 66% were male, and 6.4% died in the intensive care unit. The incidence rate of death in patients exposed to hypoglycemia was 40 per 1000 intensive care unit days compared with 17 per 1000 intensive care unit days in patients without exposure. The adjusted incidence rate ratio for intensive care unit death was 2.1 (95% confidence interval, 1.6-2.8; p < .001). CONCLUSIONS: Hypoglycemia is related to intensive care unit mortality, also when adjusted for a daily adjudicated measure of disease severity, indicating the possibility of a causal relationship.

No apparent impact of increased post-operative blood glucose levels on clinical outcome in kidney transplant recipients.

BACKGROUND: Our objective is to evaluate whether hyperglycemia in the first 48 h after renal transplantation is independently associated with rejection, post-operative infection and post-transplant diabetes mellitus (PTDM) in a retrospective cohort study. METHODS: Patients who received a renal transplant in our hospital in 2003 or 2004 were included. Glucose values until 48 h after surgery were retrieved from laboratory reports. Biopsy proven acute rejection, culture proven infections and PTDM were scored until four months after transplantation. Data were analyzed using univariate analysis and logistic multivariate analysis. RESULTS: At least one post-operative glucose value could be retrieved for 150/151 patients. Rejection occurred in 46/150 (30.5%), infection in 47/150 (31.1%) and PTDM in 19/150 (12.6%) patients. When corrected for other risk factors, no relation was found between post-operative glucose levels and rejection (weak inverse relation, OR = 0.82; 95% CI = 0.65-1.03; p = 0.09), post-operative glucose and infections (OR = 0.98; 95% CI = 0.80-1.21; p = 0.84) and post-operative glucose and PTDM (OR = 0.93; 95% CI = 0.70-1.23; p = 0.63). CONCLUSION: Increased post-operative blood glucose levels after renal transplantation were not found to be a risk factor for graft rejection. Also, post-operative glucose levels were not found to be associated with PTDM and post-operative infections.

Different routes of insulin administration do not influence serum free thiols in type 1 diabetes mellitus.

AIMS: Intraperitoneal (IP) insulin administration is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As the IP route of insulin administration mimics the physiology more closely than the subcutaneous (SC) route, we hypothesized that IP insulin would result in less oxidative stress (expressed as systemic level of free sulphydryl (R-SH) content) compared to SC insulin in subjects with T1DM. MATERIALS AND METHODS: Prospective, observational case-control study. Serum thiol measurements were performed at baseline and at 26 weeks in age- and gender-matched patients with T1DM. Serum-free thiols, compounds with a R-SH group that are readily oxidized by reactive oxygen species, are considered to be a marker of systemic redox status. RESULTS: A total of 176 patients, 39 of which used IP and 141 SC insulin therapy were analysed. Mean baseline R-SH concentration was 248 (31) µmol/L. In multivariable analysis, the route of insulin therapy had no impact on baseline R-SH levels. The estimated geometric mean concentrations of R-SH did not differ significantly between both groups: 264 (95% CI 257, 270) for the IP group and 258 (95% CI 254, 261) for the SC group with a difference of 6 (95% CI -2, 14) µmol/L. CONCLUSIONS: Based on R-SH as a marker of systemic oxidative stress, these findings demonstrate that the route of insulin administration, IP or SC, does not influence systemic redox status in patients with T1DM.

Hypoglycemia and strict glycemic control in critically ill patients.

PURPOSE OF REVIEW: In contrast to patients with diabetes mellitus, data on consequences of hypoglycemia in critically ill patients are sparse. The purpose of this review is to summarize available data on prevalence of hypoglycemia, risk factors, and possible consequences of hypoglycemia in critically ill patients. RECENT FINDINGS: There is strong evidence that strict glycemic control is beneficial for critically ill patients. Recent attempts to confirm these findings have not succeeded. Instead, they have increased the fear for negative consequences of hypoglycemia. Hypoglycemia is four to seven times more frequent in patients treated with strict glycemic control. Risk factors for hypoglycemia are a change in nutrition without adjustment of insulin treatment, diabetes mellitus, sepsis, shock, liver failure, and the need for renal replacement therapy. Consequences of hypoglycemia in critically ill patients are not well defined, but overall current evidence suggests that beneficial effects of strict glycemic control outweigh possible negative effects of hypoglycemia. SUMMARY: Hypoglycemia should be avoided in critically ill patients, but not at the cost of less stringent glycemic control. Strict glycemic control with a low incidence of hypoglycemia can be achieved with a validated (computerized) algorithm and increased surveillance in patients with an increased risk for hypoglycemia.

Impact of hyperglycemia on the efficacy of chemotherapy-A systematic review of preclinical studies.

BACKGROUND: Antineoplastic agents can provoke hyperglycemia in cancer patients with and without diabetes mellitus. We systematically reviewed the impact of hyperglycemia on the efficacy of chemotherapy. METHODS: MEDLINE was searched for preclinical intervention studies which compared chemotherapy response in hyperglycemic and euglycemic conditions. RESULTS: Thirteen preclinical studies, including 23 cell lines and 2 animal experiments were identified. In 14 cell lines and 2 animal studies, chemotherapy response was lower in a hyperglycemic (>15mmol/L) compared to a euglycemic environment (5mmol/L). The response was similar in 4 cell lines. In the remaining 5 cell lines, the hyperglycemic environment potentiated chemotherapy efficacy. CONCLUSION: Hyperglycemia attenuated the antiproliferative effect of chemotherapy in preclinical experiments, but the results are inconsistent. Whether hyperglycemia influences efficacy of chemotherapy in patients needs to be explored.

Early postoperative hyperglycaemia is not a risk factor for infectious complications and prolonged in-hospital stay in patients undergoing oesophagectomy: a retrospective analysis of a prospective trial.

INTRODUCTION: Treating hyperglycaemia in hospitalized patients has proven to be beneficial, particularly in those with obstructive vascular disease. In a cohort of patients undergoing resection for oesophageal carcinoma (a group of patients with severe surgical stress but a low prevalence of vascular disease), we investigated whether early postoperative hyperglycaemia is associated with increased incidence of infectious complications and prolonged in-hospital stay. METHODS: Postoperative glucose values up to 48 hours after surgery were retrieved for 151 patients with American Society of Anesthesiologists class I or II who had been previously included in a randomized trial conducted in a tertiary referral hospital. Multivariate regression analysis was used to define the independent contribution of possible risk factors selected by univariate analysis. RESULTS: In univariate regression analysis, postoperative glucose levels were associated with increased length of in-hospital stay (P < 0.001) but not with infectious complications (P = 0.21). However, postoperative glucose concentration was not found to be an independent risk factor for prolonged in-hospital stay in multivariate analysis (P = 0.20). CONCLUSION: Our data indicate that postoperative hyperglycaemia is more likely to be a risk marker than a risk factor in patients undergoing highly invasive surgery for oesophageal cancer. We hypothesize that patients with a low prevalence of vascular disease may benefit less from intensive insulin therapy.

Predisposing factors for hypoglycemia in the intensive care unit.

OBJECTIVE: The introduction of strict glycemic control in the intensive care unit has increased the risk for hypoglycemia. In this study we examined the association between predefined circumstances and the occurrence of hypoglycemia in the intensive care unit. DESIGN: : Retrospective cohort study. SETTING: Academic medical center. PATIENTS: All episodes of hypoglycemia (glucose value <45 mg/dL) in our intensive care unit between September 2002 and September 2004 were identified. Presence of predefined circumstances previously associated with hypoglycemia was scored around the moment of hypoglycemia using a patient data management system and in-hospital charts. Patients with a first hypoglycemic event were contrasted to controls from the same cohort, who were matched for time since admission, to correct for the effect of length of stay. Data were analyzed using conditional logistic regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,272 patients, 156 (6.9%) experienced at least one episode of hypoglycemia. Continuous venovenous hemofiltration with bicarbonate-based substitution fluid (odds ratio [OR], 14; 95% confidence interval [CI], 1.8-106), a decrease of nutrition without adjustment for insulin infusion (OR, 6.6; 95% CI, 1.9-23), diabetes mellitus (OR, 2.6; 95% CI, 1.5-4.7), insulin use (OR, 5.3; 95% CI, 2.8-11), sepsis (OR, 2.2; 95% CI, 1.2-4.1), and inotropic support (OR, 1.8; 95% CI, 1.1-2.9) were associated with hypoglycemia. Simultaneous octreotide and insulin use (OR, 6.0; 95% CI, 0.72-50) may also be associated with hypoglycemia. Gastric residual during enteral nutrition without adjusting insulin infusion, liver failure, continuous venovenous hemofiltration with lactate-based substitution fluid, diminished glomerular filtration rate, dose diminishment of glucocorticoids or catecholamines, and use of beta-blocking agents were not associated with hypoglycemia. Adjusting for age, gender, and Acute Physiology and Chronic Health Evaluation II score at admission did not materially change ORs. CONCLUSION: Use of bicarbonate-based substitution fluid during continuous venovenous hemofiltration, a decrease of nutrition without adjustment for insulin infusion, a prior diagnosis of diabetes mellitus, sepsis, and need for inotropic support were found to be associated with hypoglycemia. Simultaneous use of insulin and octreotide may be associated with hypoglycemia.

Evaluation of short-term consequences of hypoglycemia in an intensive care unit.

BACKGROUND: Introduction of strict glycemic control has increased the risk for hypoglycemia in the intensive care unit. Little is known about the consequences of hypoglycemia in this setting. We examined short-term consequences (seizures, coma, and death) of hypoglycemia in the intensive care unit. PATIENTS AND METHODS: All occurrences of hypoglycemia (glucose of <45 mg/dL) in our intensive care unit between September 1, 2002, and September 1, 2004, were identified. Patients with hypoglycemia (n = 156) were matched for time to hypoglycemia with control patients drawn from the at-risk population (nested case control method). Seizures observed within 8 hrs after hypoglycemia were scored. Discharge summaries for cases and controls were reviewed for occurrence of possible hypoglycemia-associated coma and death. A hazard ratio for in-hospital death was calculated with Cox regression analysis. RESULTS: The hazard ratio for in-hospital death was 1.03 (95% confidence interval, 0.68-1.56; p = .88) in patients with a first occurrence of hypoglycemia relative to the controls without hypoglycemia, corrected for duration of intensive care unit admittance before hypoglycemia, age, sex, and Acute Physiology and Chronic Health Evaluation II score at admission. No cases of hypoglycemia-associated death were reported. Hypoglycemic coma was reported in two patients. Seizures after hypoglycemia were observed in one patient. CONCLUSIONS: In this study, no association between incidental hypoglycemia and mortality was found. However, this data set is too small to definitely exclude the possibility that hypoglycemia is associated with intensive care unit mortality. In three patients with possible hypoglycemia-associated coma or seizures, a causal role for hypoglycemia seemed likely but could not fully be established.