Stress-induced severe transient hypercortisolism with reversible bilateral adrenal enlargement after cardiogenic shock.

Summary: Acute illness-related stress can result in severe hypercortisolism and bilateral adrenal enlargement in certain patients. We report a case of stress-induced hypercortisolism and bilateral adrenal enlargement in a patient admitted for acute respiratory distress and cardiogenic shock. Bilateral adrenal enlargement and hypercortisolism found during hospitalization for acute illness resolved 3 weeks later following the resolution of acute illness. Acute illness can be a precipitating factor for stress-induced hypercortisolism and bilateral adrenal enlargement. We hypothesize that increased adrenocorticotrophic hormone mediated by corticotrophin-releasing hormone from physical stress resulted in significant adrenal hyperplasia and hypercortisolism. This mechanism is downregulated once acute illness resolves. Learning points: Adrenal enlargement with abnormal adrenal function after stress is uncommon in humans; however, if present, it can have self-resolution after the acute illness is resolved. Stress induces enlargement of the adrenals, and the degree of cortisol elevation could be very massive. This process is acute, and the absence of cushingoid features is expected. Treatment efforts should be focused on treating the underlying condition.

Utilizing a quality of life tool to examine the presence of fatigue in subjects with diabetes mellitus.

Introduction: The prevalence of fatigue in patients with diabetes mellitus (DM) can be as high as 50 %. Physical, mental, and psychosocial components of fatigue negatively impact quality of life (QOL), morbidity and mortality. Several tools have been developed to address fatigue, but none specifically for measuring fatigue in DM. The aim of this study was to assess the impact of diabetes and neuropathy on fatigue using the Norfolk QOL-Fatigue (QOL-F) survey. Methods: 605 adult participants from [Anonymous] were recruited (400 subjects with type 1 or type 2 DM and 205 subjects without diabetes (controls)). All subjects completed the Norfolk QOL-F. Demographics, weight, BMI, and duration of diabetes were obtained. The Norfolk QOL-F, a 35-item validated questionnaire, assesses five domains: subjective fatigue, physical and cognitive fatigue, reduced activities, impaired activities of daily living, and depression. Results: Subjects with DM reported significantly higher fatigue total scores (52.63vs33.89, p < 0.0001) and in all five domains when compared to controls. Patients with DM with neuropathy were significantly more fatigued than those without (59.72vs27.83, p < 0.0001). Fatigue scores in patients with DM without neuropathy were similar to controls (27.83vs33.89, p = NS). In multivariate analysis, age, gender, and presence of neuropathy significantly impacted fatigue scores. Conclusions: The Norfolk QOL-F questionnaire can potentially identify the impact of chronic diseases such as diabetes on fatigue. Assessing the different components of fatigue is important for clinicians in improving disease management and outcomes. Further investigations are needed to confirm these observations in specific cohorts with other comorbidities.

War and Health Care Services Utilization for Chronic Diseases in Rural and Semiurban Areas of Tigray, Ethiopia.

Importance: The war in Tigray, Ethiopia, has disrupted the health care system of the region. However, its association with health care services disruption for chronic diseases has not been well documented. Objective: To assess the association of the war with the utilization of health care services for patients with chronic diseases. Design, Setting, and Participants: Of 135 primary health care facilities, a registry-based cross-sectional study was conducted on 44 rural and semiurban facilities of Tigray. Data on health services utilization were extracted for patients with tuberculosis, HIV, diabetes, hypertension, and psychiatric disorders in the prewar period (September 1, to October 31, 2020) and during the first phase of the war period (November 4, 2020, to June 30, 2021). Main Outcomes and Measures: Records on the number of follow-up, laboratory tests, and patients undergoing treatment of the aforementioned chronic diseases were counted during the prewar and war periods. Results: Of 4645 records of patients with chronic diseases undergoing treatment during the prewar period, 998 records (21%) indicated having treatment during the war period. Compared with the prewar period, 59 of 180 individuals (33%; 95% CI, 26%-40%) had tuberculosis, 522 of 2211 (24%; 95% CI, 22%-26%) had HIV, 228 of 1195 (19%; 95% CI, 17%-21%) had hypertension, 123 of 632 (20%; 95% CI, 16%-22%) had psychiatric disorders, and 66 of 427 (15%; 95% CI, 12%-18%) had type 2 diabetes records, which revealed continued treatment during the war period. Of 174 records of patients with type 1 diabetes in the prewar period, at 2 to 3 months into the war, the numbers dropped to 10 with 94% decline compared with prewar observations. Conclusions and Relevance: This study found that the war in Tigray has resulted in critical health care service disruption and high loss to follow-up for patients with chronic disease, likely leading to increased morbidity and mortality. Local, national, and global policymakers must understand the extent and impact of the service disruption and urge their efforts toward restoration of those services.

Cardiac and Sudomotor Autonomic Function in Subjects with Psoriasis With and Without Metabolic Syndrome.

Purpose: Studies have shown that subjects with psoriasis (PsO) are associated with an increased risk of developing metabolic syndrome (MetS), diabetes, and cardiovascular disease. In addition, MetS and diabetes are associated with autonomic dysfunction (AD). The aim of this study was to investigate cardiac and sudomotor autonomic function in subjects with PsO and without diabetes. Methods: A cross-sectional study was performed in 20 subjects with PsO, compared with age- and sex-matched 21 healthy controls, and 20 subjects with MetS. Subjects underwent skin evaluation by dermatologist, glycated hemoglobin (HbA1c), insulin, glucose, and lipid levels, sudomotor function testing with Sudoscan™ device (Impeto Medical, Paris, France), and cardiac autonomic function testing with ANSAR device (ANX 3.0; ANSAR Group, Inc., Philadelphia, PA). Quality of Life (QOL) and peripheral neurologic function were also assessed. Results: Participants with PsO were significantly more obese, had higher levels of fasting insulin and triglycerides, and were more insulin resistant when compared to controls. Subjects with PsO showed significantly worse cardiac autonomic function when compared to control and MetS groups. Sudomotor function and QOL scores were similar between the groups. Subgroup analysis of PsO subjects without MetS criteria (n = 15) showed persistent significantly deteriorated cardiac autonomic function when compared to the other two groups. Conclusion: This study suggests an association between PsO and cardiac AD, independent of the presence of overt dysglycemia and MetS. Additional larger studies are needed to clarify the significance of these findings and the relationship between PsO, AD, and metabolic disease.

The impact of war on the health system of the Tigray region in Ethiopia: an assessment.

The war in Tigray region of Ethiopia that started in November 2020 and is still ongoing has brought enormous damage to the health system. This analysis provides an assessment of the health system before and during the war. Evidence of damage was compiled from November 2020 to June 2021 from various reports by the interim government of Tigray, and also by international non-governmental organisations. Comparison was made with data from the prewar calendar year. Six months into the war, only 30% of hospitals, 17% of health centres, 11.5% of ambulances and none of the 712 health posts were functional. As of June 2021, the population in need of emergency food assistance in Tigray increased from less than one million to over 5.2 million. While the prewar performance of antenatal care, supervised delivery, postnatal care and children vaccination was 64%, 73%, 63% and 73%, respectively, but none of the services were likely to be delivered in the first 90 days of the war. A conservative estimate places the number of girls and women raped in the first 5 months of the war to be 10 000. These data indicate a widespread destruction of livelihoods and a collapse of the healthcare system. The use of hunger and rape as a weapon of war and the targeting of healthcare facilities are key components of the war. To avert worsening conditions, an immediate intervention is needed to deliver food and supplies and rehabilitate the healthcare delivery system and infrastructure.

The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

Effect of Diabetes Mellitus on Complication Rates of Coronary Artery Bypass Grafting.

Previous studies have shown that diabetes mellitus (DM) is a risk factor for postoperative coronary artery bypass grafting (CABG) complications. More contemporary studies are needed to guide revascularization decisions in DM patients. We performed a single-center study of patients who underwent CABG. Patients with no DM were compared with patients with DM, subgrouped according to whether or not DM was treated with insulin before admission (Insulin and No Insulin Groups). Multivariable logistic regression was used to determine whether DM was a significant predictor of mortality, combined postoperative events, and specific postoperative complications after controlling for other predictive clinical variables. Of 11,590 consecutive patients who underwent CABG, 5,013 (43%) had DM and 6,577 (57%) had no DM. Of the patients with DM, 3,433 (68%) were not treated with insulin and 1,580 (32%) were treated with insulin before admission. Multivariable logistic regression analyses showed that DM was not significantly associated with in-hospital mortality or combined postoperative events after considering other clinical variables. The No Insulin Group was significantly associated with stroke, and the Insulin Group was significantly associated with surgical site infection and new renal failure. In conclusion, this study of consecutively treated CABG patients shows that DM is not a predictor of in-hospital mortality or combined in-hospital postoperative events after adjusting for other clinical factors. DM is a predictor of permanent stroke, surgical site infection, and new renal failure. These findings may help with case selection and management of DM patients undergoing CABG.

Hypomagnesemia in Ethiopians with diabetes mellitus.

BACKGROUND: Magnesium, the second most abundant intracellular cation, plays a key role in cellular metabolism. Even though hypomagnesemia has been demonstrated in patients with both type 1 and type 2 diabetes elsewhere, limited information exists from African patients with diabetes mellitus. METHODS: This was a cross-sectional study to assess the prevalence of hypomagnesemia in Ethiopian patients with type 1 and type 2 diabetes. A total of 159 subjects were included in the study (44 patients had type 1 diabetes, 69 patients had type 2, and 46 were nondiabetic controls). RESULTS: The mean age (+/-standard error of the mean) of the subjects with type 1 diabetes, type 2 diabetes, and controls was 30.6+/-1.6, 51.3+/-1.3, and 29.0+/-1.7 years, respectively (P<.001). Patients with type 2 diabetes were significantly older than those with type 1 diabetes and controls. Basal C-peptide level and body mass index were also significantly higher in patients with type 2 diabetes (P<.001). The mean magnesium level was significantly lower in patients with diabetes than in controls (.84+/-.12 mmol/L vs 1.02+/-.17 mmol/L, P<.001). Hypomagnesemia was seen in 65% of the patients with diabetes. CONCLUSION: The study showed that patients with diabetes mellitus have lower levels of magnesium and are therefore at increased risk of complications related to magnesium. In light of these potential complications, we recommend periodic determination of magnesium levels and appropriate magnesium replacements.

Islet Cell Associated Autoantibodies and C-Peptide Levels in Patients with Diabetes and Symptoms of Gastroparesis.

INTRODUCTION: Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA). OBJECTIVE: To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity. DESIGN: 113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide. RESULTS: Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide. CONCLUSION: GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity. CLINICALTRIALSGOV IDENTIFIER: NCT01696747.

Glucose sensor-augmented continuous subcutaneous insulin infusion in patients with diabetic gastroparesis: An open-label pilot prospective study.

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

Lipid and lipoprotein profiles in Ethiopian patients with diabetes mellitus.

The association between dyslipidemia and diabetes mellitus is well established. Although various lipoprotein abnormalities have been described in patients with diabetes mellitus elsewhere, there is limited information from African patients. We undertook a cross-sectional study to assess the prevalence of dyslipidemia in Ethiopian patients with types 1 and 2 diabetes. A total of 193 subjects were included in the study (54 patients had type 1 diabetes mellitus, 92 patients had type 2 diabetes mellitus, and 47 were nondiabetic controls). Of these, 93 (48.6%) were men and 103 (51.4%) were women. The mean age+/-SEM for patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and controls were 29.8+/-1.4, 51.2+/-1.1, and 29.0+/-1.7 years, respectively. Hypercholesterolemia and hypertriglyceridemia, defined as cholesterol level of greater than 5.2 mmol/L and triglyceride level of greater than 1.8 mmol/L, were found in 47.3% and 41.8% of patients with diabetes mellitus compared with 27% and 17% in controls (P<.05 for both). The mean total cholesterol level+/-SEM was significantly higher in patients with type 1 or 2 diabetes mellitus than controls (5.76+/-0.27 mmol/L in type 1 diabetes mellitus, 5.25+/-0.2 mmol/L in type 2 diabetes mellitus, and 4.67+/-0.28 mmol/L in healthy controls, P<.02). Triglycerides and low-density lipoprotein levels were also significantly higher in patients with diabetes than in controls, whereas high-density lipoprotein levels were significantly lower in patients with diabetes. In conclusion, our study demonstrates that in Ethiopians with diabetes mellitus, dyslipidemia occurs more frequently than in controls. Thus, we recommend periodic screening for dyslipidemia in all Ethiopian patients with diabetes. Other studies are needed to assess the potential negative effect of dyslipidemia and obesity on morbidity and mortality in Ethiopians with diabetes.

Metastatic malignant insulinoma in a patient with type 2 diabetes mellitus: case presentation and literature review.

OBJECTIVE: To describe the occurrence of metastatic malignant insulinoma in a patient with preexisting type 2 diabetes mellitus. METHODS: We present a detailed case report, with clinical, biochemical, and imaging findings, and summarize the data from 21 similar cases in the literature. RESULTS: The occurrence of malignant insulinoma in a patient with preexisting diabetes is very rare and thus can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide levels during hypoglycemic episodes in the absence of sulfonylurea on a blood screen. Abdominal computed tomographic scan and magnetic resonance imaging revealed a pancreatic mass as well as metastatic lesions in the liver. The pancreatic mass was removed and confirmed to be a malignant insulinoma. This procedure was followed by disappearance of the hypoglycemic episodes as well as the diabetes for a few months. On follow-up, however, more metastatic lesions appeared in conjunction with a protracted course of hypoglycemia that necessitated treatment with antihypoglycemic agents and, 3 years after the initial surgical intervention, culminated in the death of the patient. CONCLUSION: Our patient is one of the few subjects known to have a malignant insulinoma in conjunction with preexisting diabetes. A high degree of suspicion for the presence of an insulinoma should be maintained when unexplained hypoglycemic episodes occur in a patient with previously stable diabetes.

Inhaled human insulin: an inspiration for patients with diabetes mellitus?

Inhaled insulin offers a novel option for controlling blood glucose levels in type 1 and type 2 diabetes, obviating the need for multiple daily injections. The first of several delivery systems, insulin Exubera, was recently approved by the US Food and Drug Administration (FDA). However, questions remain regarding its efficacy, cost-effectiveness, and possible deleterious effects on pulmonary function. This review will discuss the pharmacology, efficacy, important clinical trials, and practical aspects of inhaled insulin, and potential concerns associated with its use.

The impact of gastroparesis on diabetes control: Patient perceptions.

UNLABELLED: The impact of gastroparesis on diabetes management and control from the patient perspective has not been well characterized. The aim of this study was to identify patient perceptions regarding the impact of gastroparesis on managing their diabetes. METHODS: Patients with diabetes being referred for gastroparesis were enrolled in this prospective study. Gastroparetic symptom severity was assessed with the Patient Assessment of Upper GI Symptoms (PAGI-SYM). A questionnaire examined the impact of gastroparesis on diabetes related symptoms and control. RESULTS: 54 diabetic gastroparesis patients (36 T1DM, 18 T2DM) participated. Duration of diabetes averaged 17.4±1.4years and gastroparetic symptoms 5.1±1.1years. Patients rated their most severe symptoms as postprandial fullness, early satiety, and nausea. Two thirds of diabetic subjects identified that since their diagnosis of gastroparesis, their diabetes was more difficult to control (44 of 54 patients) and that extra time and effort were required for care of their diabetes (45 of 54). Patients with T1DM, compared to those with T2DM, more often expressed that since developing gastroparesis, their blood sugars have been higher, they have had more frequent episodes of hypoglycemia, and they found that their gastroparetic symptoms worsened if blood sugars were too high. CONCLUSIONS: Gastroparesis has a significant impact on patients' perceived ability to self-manage and control their diabetes. T1DM patients, in particular, associate their gastroparesis with episodes of hyper- and hypo-glycemia, and find their gastroparetic symptoms worsen with poor control. Future research should focus on strategies to support self-management of patients with diabetic gastroparesis.

Islet cell-associated autoantibodies in Ethiopians with diabetes mellitus.

BACKGROUND & AIMS: Our understanding of the role of autoimmunity in the pathogenesis of diabetes in African populations is limited. This study aims to evaluate the prevalence of 4 different islet cell-associated antibodies in Ethiopian patients with diabetes and non-diabetic controls. METHODS: A total of 187 subjects from a diabetic clinic at an Ethiopian hospital were evaluated in a cross-sectional study. Fifty-five patients had type 1 diabetes mellitus (T1DM), 86 had type 2 diabetes mellitus (T2DM) and 46 were non-diabetic controls. Islet cell-associated antibodies were measured using 4 different assays for antibodies against islet cells (ICA), glutamic acid decarboxylase (GADA), insulin (IAA) and the protein tyrosine phosphatase-like IA-2 (IA-2A). RESULTS: Comparing the antibody positivity in subjects with T1DM versus T2DM, the results were as follows: 29% versus 3.5% for GADA; 21% versus 2.7% for ICA; 27% versus 16% for IAA. In the control group, the only positive result was for IAA at 2%. IA-2A was absent in all groups. The combi-assay for GADA and IA-2A detected all GADA-positive subjects. T2DM patients who were GADA positive had lower BMI, lower C-peptide levels and all of them were on insulin therapy. CONCLUSIONS: Compared to Caucasians, Ethiopians with T1DM have less prevalence of islet cell-associated antibodies, but the rates are higher than in T2DM. GADA is present in Ethiopians, whereas IA-2A seems to be absent. GADA positivity in T2DM correlates with clinical features of T1DM, indicating the existence in Ethiopia of the subgroup, latent autoimmune diabetes in adults.

Raloxifene causing malabsorption of levothyroxine.

To our knowledge, raloxifene hydrochloride, a selective estrogen receptor modulator, has never been reported to interfere with absorption of levothyroxine. We describe a 79-year-old woman with chronic, treated primary hypothyroidism, presenting with increasing levothyroxine requirement while taking raloxifene at the same time as levothyroxine. For two 6- to 8-week periods, we separated the ingestion of raloxifene and levothyroxine by about 12 hours. In addition, we tested the absorption of 1.0 mg of levothyroxine sodium with and without the coadministration of 60 mg of raloxifene hydrochloride on 2 separate occasions by collecting serial blood samples for 6 hours. Hypothyroidism occurred in a reproducible fashion whenever levothyroxine and raloxifene were administered together and improved whenever they were taken separately. Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone. By a yet unknown mechanism, raloxifene caused malabsorption of levothyroxine in our patient when coadministered.