Diabetic Ketoacidosis Management and Treatment Outcome at Medical Ward of Shashemene Referral Hospital, Ethiopia: A Retrospective Study

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.

Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases

Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

Multicenter, Open-Label, 2-Arm, Pilot Trial for Safe Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for a RISING-STAR Trial

Background: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. Methods: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.

A Review of Coumarins and Coumarin-Related Compounds for Their Potential Antidiabetic Effect

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.

The Relationship Between Thyroid Function and Body Composition, Leptin, Adiponectin, and Insulin Sensitivity in Morbidly Obese Euthyroid Subjects Compared to Non-obese Subjects

Background/Objectives: Thyroid function tests (TFTs) changes in obese people have been studied with increasing interest, however, studies have been inconsistent hence it remains poorly understood. We compared the TFTs of morbidly obese euthyroid Saudi subjects with non-obese controls and then we examined the influence of leptin, adiponectin, and insulin resistance on TFTs. Subjects/Methods: Fifty-five euthyroid obese subjects attending bariatric surgery clinic and 52 non-obese age-and gender-matched controls were recruited. We measured body weight, BMI, body composition, thyroid-stimulating hormone (TSH), Free T4 (FT4), Free T3(FT3), thyroid antibodies, fasting leptin, adiponectin, and lipid profile. Insulin resistance was quantified by HOMA-IR. Data are presented as mean ± SEM. Results: Mean BMI was 45.6 ± 1.5 and 23.2 ± 0.5 kg/m2, for the obese and non-obese controls, respectively, P value < 0.001. Mean TSH was 2.7 ± 0.18 mIU/L in obese subjects and 1.7 ± 0.13 mIU/L (0.27-4.2) in the non-obese controls, respectively, P value .014. Mean FT3 was 3.9 ± 0.1 pmol/L (3.1-6.8) in obese subjects compared to 5.0 ± 0.1 pmol/L in non-obese controls, respectively, P value 0.001, however, FT4 was similar in the 2 groups. In the whole group ( N = 107), BMI correlated positively with TSH and negatively with FT3. Leptin correlated negatively with both FT4 and FT3 in the non-obese group only while none of the TFTs correlated with HOMA-IR or adiponectin in either group. Binary logistic regression showed that each 1 unit increase in TSH increased the odds of becoming obese by 12.7, P value 0.009, 95 C.I. (1.9-85.0). Conversely, each - unit increase in FT3 decreased the odds of becoming obese by 0.2, P value 0.023, 95% C.I. (0.05-0.80). Conclusions: We report a small increase in TSH and a small decrease in FT3 within the normal range in obese subjects compared to non-obese controls. We also report a positive correlation between TSH and BMI with increased odds ratio of becoming obese with the increase in TSH and decrease in FT3. These changes may be either causally related or adaptive to the obesity state. FT4 and FT3 seem to correlate with leptin (but not with adiponectin or HOMA-IR) in the non-obese controls only. Larger mechanistic studies are needed to further elucidate the interesting association between obesity and TFTs.

Quality of Life and Glycemic Control in Saudi Children with Type 1 Diabetes at Different Developmental Age Groups

Background: Children with type 1 diabetes (T1D) at different stages of development have age-specific needs, which can influence their perception of quality of life (QoL). In our study, we aimed to emphasize these age-specific needs and assess the perception of QoL in Saudi children with T1D, as well as their parents correlating QoL scores with children’s glycemic control. Methods: This is a cross-sectional study in which children with T1D and their parents from 2 tertiary institutes in Saudi Arabia have answered a standard diabetes-specific QoL questionnaire (PedsQL™ 3.0 diabetes module, translated in Arabic). We also reported glycated hemoglobin (HbA1c) results for these children within a month of completing the questionnaire. The QoL total aggregate and domain scores for self (children) and proxy (parents’) reports were compared and correlated with children’s HbA1c. Results: A sample was 288 self and proxy reports from 144 children with T1D of 3 age groups: 5 to 7 years (7%), 8 to 12 years (49%), and 13 to 18 years (44%), and their parents. QoL differed significantly between self and proxy reports in the total aggregate and domain scores ( P-values range from .02 to <.001). The impact on QoL was significantly higher in female patients ( P = .043). Insulin pump users had better HbA1c ( P = .007), and HbA1c level was worse in those who intended to fast at Ramadan ( P = .005). Conclusion: Children with T1D at different developmental age groups perceive QoL differently than their parents. Adjusting management as per age-specific challenges could potentially improve these children’s QoL and glycemic control.

Glycemic Variability in Type 1 Diabetes Mellitus Saudis Using Ambulatory Glucose Profile

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.

Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control

Dipeptidyl peptidase (DPP)-4 inhibitors are oral anti-diabetic medications that block the activity of the ubiquitous enzyme DPP-4. Inhibition of this enzyme increases the level of circulating active glucagon-like peptide (GLP)-1 secreted from L-cells in the small intestine. GLP-1 increases the glucose level, dependent on insulin secretion from pancreatic β-cells; it also decreases the abnormally increased level of glucagon, eventually decreasing the blood glucose level in patients with type 2 diabetes. DPP-4 is involved in many physiological processes other than the degradation of GLP-1. Therefore, the inhibition of DPP-4 may have numerous effects beyond glucose control. In this article, we review the pleiotropic effects of DPP-4 inhibitors beyond glucose control, including their strong beneficial effects on the stress induced accelerated senescence of vascular cells, and the possible clinical implications of these effects.

Sedentary Behavior Counseling Intervention in Aging People With Type 2 Diabetes: A Feasibility Study

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.

A Community Pharmacy-Based Intervention in the Matrix of Type 2 Diabetes Mellitus Outcomes (CPBI-T2DM): A Cluster Randomized Controlled Trial

Introduction: Egypt has the ninth highest diabetes mellitus (DM) prevalence in the world. There is a growing interest in community involvement in DM management. Aim of the study: The aim of the study was to evaluate the tailored diabetes care model (DCM) implementation in Alexandria governorate by community pharmacy-based intervention (CPBI) from a clinical, humanistic, and economic aspect. Methods: This is a 6-month period cross-over cluster randomized control trial conducted in Alexandria. Ten clusters owing 10 community pharmacies (CPs) recruited 100 health insurance-deprived T2DM patients with >7% HbA1c in 6-months. The study was divided into 2 phases (3 months for each period) with a 1-month washout period in between. After CPs training on DCM, the interventional group received pictorial training for 45 minutes in first visit, and 15 minutes in weekly visits, whereas the control group patients received the usual care (UC). At baseline and end of each phase (3 months), patients had clinical and physical activity assessments, filled all forms of study questionnaire (knowledge, self-management, satisfaction, and adherence) and did all laboratory investigations (Fasting Blood Glucose [FBG]), HbA1c, protein-creatinine clearance (PCR), creatine clearance (GFR), and lipid profile. Results: There was no significant difference in the basal systolic and diastolic blood pressure between patients in the CBPI and UC groups, but the CBPI had significantly decreased the mean SBP and DBP by ( P = .008, .040, respectively). Also, significant waist circumference and BMI reductions (−5.82 cm and −1.86 kg/m2, P = .001) were observed in the CBPI. The CBPI patients achieved a greater reduction in FBG and HbA1C than the UC patients (102 mg/dL and 1.9%, respectively P < .001). Also, significant reductions in total cholesterol, LDL, and triglyceride (−6.4, −15.4, and −6.3 mg/dL respectively, P = .001) were achieved in the CBPI group. No significant differences were found in HDL, GFR, and PCR. Moreover, significant improvements of behavior, score of knowledge, self-management, satisfaction, and adherence were observed in CBPI patients. After multivariate analysis, HbA1C readings were significantly influenced by baseline HbA1C and eating habits. The cost saving for CPBI was −1581 LE per 1% HbA1c reduction. Conclusion: This is the first study in Egypt that illustrated the positive impact of pictorial DCM delivered by CPBI collaborative care on clinical, humanistic, laboratory, and economic outcomes to local T2DM patients.