Clinical Medicine Insights-Endocrinology and Diabetes最新文献

Background and aims: Worldwide, type 2 diabetes mellitus accounts for a considerable burden of disease, with an estimated global cost of >800 billion USD annually. For this reason, the search for more effective and efficient therapeutic anti-diabetic agents is continuing. Coumarins are naturally derived and synthetic molecules with a wide variety of biological actions. The most common application of these molecules in medicine is for their thrombostatic activity. This study aims to give an overview of the current knowledge about the applicability of these chemical products in the therapeutic strategy against diabetes and its complications.

Methods: For this purpose, we searched internet databases for publications and abstracts in English that investigated the effects of coumarins or coumarin-like agents with potential anti-diabetic activity.

Results: The result is that a variety of these agents have proven in in vitro, in silico, and simple animal models to possess properties that may reduce the glucose absorption rate in the intestines, increase the level of insulin, increase the cellular uptake of glucose or reduce the gluconeogenesis. In addition, some of these agents also reduced the level of glycation of peptides in diabetic animal models and showed antioxidant properties.

Conclusion: In conclusion, we can summarize that coumarins and their related derivatives may be potential antidiabetic agents. Useful formulations with appropriate pharmacokinetic and pharmacodynamic properties must be developed and tested for their efficacy and toxicity in comprehensive animal models before they can enter clinical trials.

This study examined the feasibility and effect of sedentary behavior (SB) counseling on total sitting time (TST) and glycemic control in people with type 2 diabetes (T2D). Community-dwelling sedentary adults with T2D (n = 10; 8 women; age 65.6 ± 7.31) completed SB counseling (motivational interviewing-informed education about SB) aided by an activity monitor with a vibrotactile feature (activPAL3TM). The monitor was worn for 7 days, on weeks 1 and 13 (without the vibrotactile feature) and during weeks 5 and 9 (with the vibrotactile feature). Intervention feasibility was determined by study retention rates and activity monitor tolerability, and differences between pre- and post-intervention average daily TST. Paired t-test were performed. The effect size (ES) was calculated using Cohen d. All participants attended all study sessions with only 20% reporting moderate issues tolerating the activity monitor. TST time decreased from 11.8 hours ± 1.76 at baseline to 10.29 hours ± 1.84 at 3 months' assessment (P < .05) with a large ES (Cohen d = .88). HbA1c was decreased by 0.51% (P < .05) at the end of the intervention. This study found that the intervention was feasible for sedentary adults with type 2 diabetes.

Background: A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function.

Methods: In a cross-sectional study with CF patients (⩾18 years), we conducted an oral glucose tolerance test and dual energy X-ray absorptiometry scan (DXA). Based on plasma glucose, glucose tolerance was defined as normal (NGT): 1-hour <11.1 mmol/L and 2-hour <7.8 mmol/L, impaired (IGT): 2-hour ⩾7.8 and <11.1 mmol/L or CFRD: 2-hour ⩾11.1 mmol/L. Insulin resistance (HOMA-IR) was derived from fasting levels of plasma glucose and plasma insulin, and fat-free and fat mass index (kg/m²) from DXA. Associations were evaluated using linear regression models adjusted for age, sex, and pancreas insufficiency.

Results: Among 79 CF patients with exocrine pancreas insufficiency, impairment of glucose tolerance corresponded to reduced insulin secretion. In the IGT group the fat-free mass index (FFMI) was 1.2 kg/m² (95% CI: [-2.3, -0.03] kg/m², P = .044) lower compared to the NGT group. FFMI increased insignificantly by 0.4 kg/m² (95% CI: [-0.6, 1.5] kg/m², P = .422) among the insulin-treated CFRD group compared to IGT. Fat mass index (FMI) was not different between groups but tended to decrease with glucose tolerance impairment. For each 100 pmol/L increase in fasting insulin FFMI increased by 1.77 kg/m² (95% CI: [0.21, 3.33] kg/m²/pmol/L/100) and FMI increased by 6.15 kg/m² (95% CI: [3.87, 8.44] kg/m²/pmol/L/100). In multivariate analyses, HOMA-IR was positively associated with FFMI (β = 0.5 kg/m²/HOMA-IR, 95% CI: [0.08, 0.92] kg/m²/HOMA-IR, P = .021) and FMI (β = 1.5 kg/m²/HOMA-IR, 95% CI: [0.87, 2.15] kg/m²/HOMA-IR, P < .001).

Conclusions: Muscle mass was significantly lower among participants with impaired glucose tolerance (IGT), while muscle mass was normalized among those treated with insulin.

Background: To evaluate the clinical characteristics, treatment patterns, and clinical effectiveness and safety of high doses of metformin (1500-2500 mg/day) in Indian adults with type 2 diabetes mellitus (T2DM).

Materials and methods: A retrospective, multicentric (n = 241), real-world study included patients with T2DM (aged >18 years) receiving high doses of metformin. Details were retrieved from patient's medical records.

Results: Out of 5695 patients, 62.7% were men with median age was 50.0 years. Hypertension (67.5%) and dyslipidemia (48.7%) were the prevalent comorbidities. Doses of 2000 mg (57.4%) and 1500 mg (29.1%) were the most commonly used doses of metformin and median duration of high-dose metformin therapy was 24.0 months. Metformin twice daily was the most frequently used dosage pattern (94.2%). Up-titration of doses was done in 96.8% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.08%; P < .001). The target glycemic control was achieved in 91.2% patients. A total of 83.0% had decreased weight. Adverse events were reported in 156 patients. Physician global evaluation of efficacy and tolerability showed majority of patients on a good to excellent scale (98.2% and 97.7%).

Conclusion: Clinical effectiveness and safety of a high-dose metformin was demonstrated through significant improvement in HbA1c levels and weight reduction.

Cystic fibrosis-related diabetes mellitus (CFRD) is the most common non-pulmonary co-morbidity in cystic fibrosis (CF). CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which leads to aberrant luminal fluid secretions in organs such as the lungs and pancreas. How dysfunctional CFTR leads to CFRD is still under debate. Both intrinsic effects of dysfunctional CFTR in hormone secreting cells of the islets and effects of exocrine damage have been proposed. In the current review, we discuss these non-mutually exclusive hypotheses with a special focus on how dysfunctional CFTR in endocrine cells may contribute to an altered glucose homeostasis. We outline the proposed role of CFTR in the molecular pathways of β-cell insulin secretion and α-cell glucagon secretion, and touch upon the importance of the exocrine pancreas and intra-pancreatic crosstalk for proper islet function.

Cushing's syndrome causes increased morbidity and mortality due to cardiovascular and infectious diseases. Exogenous Cushing's syndrome can render the adrenal glands unable to cope with severe infections and may result in Addisonian crisis, which can be fatal if not properly diagnosed and treated. During hospitalization for disease exacerbation, a man on chronic glucocorticoid therapy for Crohn's disease and Cushingoid features developed polymicrobial septic shock together with hypotension that was unresponsive to fluids. On suspicion of relative adrenal insufficiency (cortisol levels were "inadequately" normal), intravenous hydrocortisone was started; norepinephrine was also required to normalize blood pressure. Following clinical improvement, oral cortisone acetate was started. On discharge, he was instructed on how to manage stressful events by increasing oral glucocorticoid treatment or starting a parenteral formulation, if required. Chronic glucocorticoid therapy can cause severe side-effects; in addition, hypoadrenalism can occur in critical illnesses (eg, severe infections). Prompt recognition and proper therapy of this condition can be life-saving.

Background: Stress-induced hyperprolactinemia can be difficult to differentiate from true hyperprolactinema and may result in patients having unnecessary investigations and imaging. We report the results of cannulated prolactin tests with serial prolactin measurements from an indwelling catheter to differentiate true from stress-induced hyperprolactinemia in patients with persistently mildly elevated prolactin levels in both referral and repeat samples.

Methods: Data were collected for 42 patients who had a cannulated prolactin test between January 2017 and May 2018. After cannula insertion, prolactin was measured at 0, 60, and 120 minutes. Normalization is defined as a decline in prolactin to gender-defined normal ranges.

Results: The mean age was 33.8 years (SD ± 9.9), and 37 (88%) were female. Menstrual irregularities were the main presenting symptom in 28.57% of the patients. Prolactin normalized in 12 (28.6%) patients of whom cannulated prolactin test was done. Repeat random prolactin levels were significantly higher in patients whose prolactin did not normalize during the cannulated prolactin test. MRI of the pituitary gland showed an abnormality in 23 out of 28 (82%) patients who did not normalize prolactin, a microadenoma in the majority of patients (18 patients).

Conclusion: The cannulated prolactin test was useful in excluding true hyperprolactinemia in 28.6% of patients with previously confirmed mildly elevated random prolactin on two occasions, thus avoiding over-diagnosis and unnecessary imaging.

Background: Glucose variability (GV) is a common and challenging clinical entity in the management of people with type 1 diabetes (T1DM). The magnitude of GV in Saudi people with T1DM was not addressed before. Therefore, we aimed to study GV in a consecutive cohort of Saudis with T1DM.

Methods: We prospectively assessed interstitial glucose using FreeStyle^® Libre flash glucose monitoring in people with TIDM who attended follow-up in the diabetes clinics at King Fahad Medical City between March and June 2017. Glycemia profile, standard deviation (SD), coefficient of variation (CV), mean of daily differences (MODD), and mean amplitude of glucose excursion (MAGE) were measured using the standard equations over a period of 2 weeks.

Results: Fifty T1DM subjects (20 males) with mean age 20.2 ± 6.1 years and mean fortnight glucose 192 ± 42.3 mg/dl were included. The mean SD of 2-week glucose readings was 100.4 ± 36.3 mg/dl and CV was 52.1% ± 13%. Higher levels of glucose excursions were also observed. MODD and MAGE were recorded as 104.5 ± 51.7 and 189 ± 54.9 mg/dl, respectively which is 2 to 4 times higher than the international standards. Higher MODD and MAGE were observed on weekends compared to weekdays (111.3 ± 62.1 vs 98.6 ± 56.2 mg/dl and 196.4 ± 64.6 vs 181.7 ± 52.4 mg/dl, respectively; P ⩽ .001).

Conclusion: Higher degree of glycemic variability was observed in this cohort of TIDM Saudis. Weekends were associated with higher glucose swings than weekdays. More studies are needed to explore these findings further.

Autoimmune polyendocrine syndromes (APS) are a heterogeneous group of diseases characterized by the presence of autoimmune dysfunction of 2 or more endocrine glands and other non-endocrine organs. The components of the syndrome can manifest throughout life: in childhood-APS type 1 (the juvenile type) and in adulthood-APS type 2, 3, and 4 (the adult types). Adult types of APS are more common in clinical practice. It is a polygenic disease associated with abnormalities in genes encoding key regulatory proteins of the major histocompatibility complex (MHC). The search of for candidate genes responsible for mutations in adult APS is continuing. Genetic predisposition is insufficient for the manifestation of the APS of adults, since the penetrance of the disease, even among monozygotic twins, does not approach 100% (30-70%). The article presents the case of isolated Addison's disease and APS type 2 in monozygotic twins with a revealed compound heterozygosity in the candidate gene VTCN1.

Background: Diabetic Ketoacidosis (DKA) is the most common and yet potentially life-threatening acute complication of diabetes that progresses rapidly to death and requires immediate medical intervention.

Objective: To assess the DKA management and treatment outcome/in-hospital mortality and its predictors among hospitalized patients with DKA at the Medical ward of Shashemene Referral Hospital (SRH).

Method: A retrospective study was conducted at the Medical Ward of SRH from 01 February 2015 to 31 January 2017. A systematic random sampling technique was used to select study subjects based on the inclusion criteria. Thus, of 236 reviewed charts, only 225 patients with DKA fulfilled inclusion criteria. Treatment outcome was considered good for patients who have shown improvement at discharge, while poor for patients who left against medical advice or died in the hospital. Logistic regression analysis was done to determine independent predictors for treatment outcome/in-hospital mortality using SPSS version 20 with statistical significant at P ⩽ .05.

Results: Of 225 patients with DKA, 124 (55.1%) were male. Regular insulin was prescribed to all patients and antibiotics were administered to 87 (38.7%). Potassium supplementation was given only for 28 (12.4%). Non-adherence to insulin treatment (n = 91; 40.4%) and infection (n = 66; 29.3%) were the principal DKA precipitating factors. Even though 73.8% of hospitalized patients with DKA have shown good treatment outcomes, DKA contributed 12% in-hospital mortality. The result of multivariate logistic regression analysis shown that hypoglycemia is the only independent predictor for in-hospital mortality[P = .03]. Moreover, the independent predictors for poor DKA treatment outcome were found to be smoker [P = .04], Urinary tract infection (UTI) relative to other co-morbid condition [P < .001], severe hypokalemia which increase risk of poor treatment outcome by around 4 times [P = .02], and use of Metronidazole as a concurrent medication relative to other concurrent medication [P = .03].

Conclusion: There was a high in-hospital mortality rate due to correctable causes. This mortality is unacceptable as it was majorly related to the poor practice of potassium supplementation and hypoglycemia due to insulin. Thus, clinicians and stakeholders should have to focus on modifiable factors (hypokalemia, UTI, and hypoglycemia) to reduce poor treatment outcome/in-hospital mortality.