Martins IJ. Appetite dysregulation and the apelinergic system are connected to the global chronic disease epidemic. Series Endo Diab Met. 2020;1(3):67-69.
Article DOI: 10.54178/jsedmv1i3003
Series of Endocrinology, Diabetes and Metabolism
Mikhail N. Oral semaglutide for the treatment of type 2 diabetes: a mini review. Series Endo Diab Met. 2019;1(3):62-66.
Objective: To review efficacy and safety of the first orally available glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide.
Methods: PubMed search published in English, French and Spanish from January 2000 until September 04, 2019. Search terms included “oral semaglutide”, “semaglutide”, “GLP-1 receptors”, “clinical trials”, “absorption”, “metabolism”, “efficacy”, “safety”, “cardiovascular”, “kidney disease”. Randomized trials, review articles, expert opinions and editorials are included in the review.
Results: Oral semaglutide is effectively absorbed in the stomach by absorption enhancer, but has to be taken in the fasting state with water, and no food allowed for 30 min after intake. It is generally comparable in efficacy to the subcutaneous form of semaglutide. When compared to liraglutide, oral semaglutide is slightly superior in decreasing hemoglobin A1c (HbA1c) (-0.3% vs. liraglutide) and weight (-1.3 kg vs. liraglutide), but is associated with more frequent adverse effects (reported by 80% vs. 74% of patients). Oral semaglutide was more effective than sitagliptin. Limited data suggest that oral semaglutide is safe and effective in patients with moderate degree of renal impairment. A large randomized trial of median follow-up of 15.9 months, showed that oral semaglutide was non-inferior to placebo in terms of cardiovascular events and mortality, and might have beneficial effects on reducing some of these events.
Conclusion: Oral semaglutide has an efficacy and safety profile consistent with the class of GLP-1 receptor agonists. It represents a useful therapeutic option for patients with type 2 diabetes who are reluctant to take injections. Further studies are needed to establish its long-term efficacy and safety in a large population of type 2 diabetes, including those with chronic kidney disease.
Article DOI: 10.54178/jsedmv1i3002
Reiter RJ, Rosales-Corral SA. Melatonin reprograms glucose metabolism in cancer cell mitochondria. Series Endo Diab Met. 2019;1(3):52-61.
Melatonin has a long history of studies which confirm its ability to inhibit cancer growth. Melatonin is present in high concentrations in the mitochondria of normal cells but is likely absent from the mitochondria of cancer cells, at least when isolated from tumors harvested during the day. Herein, we hypothesize that melatonin’s absence from cancer cell mitochondria prevents these organelles from metabolizing pyruvate to acetyl coenzyme A (acetyl-CoA) due to suppression of the activity of the enzyme pyruvate dehydrogenase complex (PDC), the enzyme that catalyzes the conversion of pyruvate to acetyl-CoA. This causes cancer cells to metabolize glucose to lactate in the cytosol (the Warburg effect). Since cancer cell mitochondria can take up nighttime pineal-derived melatonin from the blood, the indoleamine predictably promotes the conversion of pyruvate to acetyl-CoA in the mitochondria during the night. Thus, while cancer cells exhibit a typical cancer phenotype during the day, at night cancer cells have a more normal cell phenotype. Via similar actions, melatonin probably overcomes the insensitivity of cancers to chemotherapies. Hopefully, the hypothetical processes proposed herein will soon be experimentally tested.
Article DOI: 10.54178/jsedmv1i3001
Mutonga DM, Mureithi MW, Ngugi NN, et al. Diabetic foot ulcers in a Kenyan referral and teaching hospital: risk factors, patient characteristics and clinical outcomes. Series Endo Diab Met. 2019;1(2):41-51.
Introduction: The burden of diabetes mellitus (DM) is increasing in resource-poor settings leading to a rise in diabetic complications. Foot complications result in almost half of all hospital admissions among diabetic patients and may result in amputations or death.
Objective: To investigate the sociodemographic, clinic-laboratory characteristics and clinical outcomes of patients with diabetic foot ulcers (DFU) in a clinical setting.
Materials and Methods: A cross-sectional study of 84 adult consecutive inpatients and outpatients at Kenyatta National Hospital (KNH) with any type of DM and having active DFU was conducted over 12 months. History and physical examinations findings were recorded through a structured questionnaire. Relevant data on the most recent blood tests and clinical outcomes for patients with foot ulcers were retrieved from the patients’ medical notes and analysed.
Results: Majority (68%) were inpatients. The mean age was 60.30 years with 68% living in urban areas and 60% having minimal or no formal education. 8% were newly diagnosed with DM. The median duration of DM was 6.5 years. A majority (96%) had type 2 diabetes mellitus (T2DM). 45% were on insulin only, 18% on oral drugs only and 32% on a combination of both. The median random blood sugar was 9.60 mmol/L and glycated haemoglobin was 8.80%. Although 61% of patients had co-morbid hypertension, only about 40% had elevated systolic blood pressure (BP) while 23% had elevated diastolic pressures. A majority of the patients had good lipid profile, 85% with desirable total cholesterol and 70% having ideal low-density lipoproteins. The mortality rate among patients with DFU was 11%.
Conclusion: There are poor outcomes for patients with DFU in this setting such as poor wound healing, high recurrence rates, increased amputations and mortality compared to previous studies. However, the prevalence of uncontrolled hypertension, dyslipidaemia and neuropathy was much lower than earlier local reports.
Article DOI: 10.54178/jsedmv1i2004
Morshed S, Jahan S, Hasan M, et al. Sclerosteosis: a rare, sclerosing bone dysplasia in a Bangladeshi male. Series Endo Diab Met. 2019;1(2):35-40.
We report a 26-year-old male who was initially diagnosed as osteopetrosis and referred for endocrine evaluations. But due to specific clinical features supported by investigations, we diagnosed the case as sclerosteosis. The patient was managed by a multidisciplinary team approach. Sclerosteosis may be erroneously diagnosed as osteopetrosis. However, many unique features make it a separate entity.
Article DOI: 10.54178/jsedmv1i2003
Kaur KK, Allahbadia G, Singh M. How to classify type 2 diabetes mellitus and approach its treatment in view of associated diabetes and complications-a short communication. Series Endo Diab Met. 2019;1(2):29-34.
With the increase in epidemic of obesity, the incidence of type 2 diabetes mellitus (T2DM) is increasing globally so much that the need has arisen for treating the two diseases together with the term diabesity getting coined. Here, we have tried to sub-classify T2DM stage-wise and how the treatment should be aimed keeping in view the use of weight-neutral anti-diabetic drugs. Preferably, insulin needs to be avoided due to its weight gaining effects and use of liraglutide should be preferred in the heavily obese diabetics due to its weight lowering effects. If the patient is in stage 4 group where insulin is practically non-existent, one can try using anti-obesity drugs along with insulin or see which works better with the influence of bariatric surgery seen on controlling diabetes in morbidly obese subjects.
Article DOI: 10.54178/jsedmv1i2002
Sheriff DS. Gestational diabetes mellitus a dysfunctional metabolic state-a perspective. Series Endo Diab Met. 2019;1(2):24-28.
Pregnancy is considered as a test for beta cell reserve. If there is a good function, insulin resistance will overcome. If not, gestational diabetes will occur. Insulin resistance (IR) present in normal pregnancy is required to provide nutrients to the growing fetus. There is a rapid increase of insulin in such an insulin resistant state. The possibility of lipid deposition in muscle fibers (intramyocellular) could be one of the possible mechanism of IR in gestational diabetes mellitus (GDM). The poor response of insulin release, possible fat deposition in the skeletal muscle or ectopic fat deposition may cause dysfunctional homeostasis in GDM. This will definitely influence the fine tuning of metabolic machinery of a growing fetus. Children born with such subtle metabolic state will probably be more prone to glucose intolerance and ectopic lipid deposition. The finding that children born to GDM mothers are prone to glucose intolerance may be an eye-opener to monitor such children for beta cell function.
Article DOI: 10.54178/jsedmv1i2001
Aljabri KS, Bokhari SA, Alharthi TA. The relevance of insulin-like growth factor 1 concentration as a screening test for diagnosis of growth hormone deficiency. Series Endo Diab Met. 2019;1(1):16-23.
Objective: Growth hormone deficiency (GHD) is one of the most important endocrine and treatable causes of short stature. Insulin-like growth factor 1 (IGF-1) concentration is not recommended to establish the diagnosis of GHD. The aim of our study was to analyze the relevance of IGF-1 concentration as a screening test for the diagnosis of GHD.
Materials and Methods: We retrospectively studied patients who were evaluated for short stature at the Endocrinology Department of King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia from January 2015 to December 2018. For IGF-1, laboratory reference ranges were based on age and sex. For all eligible patients, IGF-1 concentration was determined and an ITT was performed. Patients with a peak GH of ≤ 5.0 ng/ml were considered to be GHD and patients with a peak GH of ≥ 5.1 ng/ml were considered non-GHD (nGHD).
Results: We retrospectively included 47 patients for analysis. Mean age was 14.7 ± 1.7 years. There were 38 males (80.9%) and 9 females (19.1%) and mean IGF-1 concentration was 146.4 ± 69.4 ng/dl. Results from the ITT indicated that 27 (57.4%) had GHD. Age was not significantly different between GHD and non-GHD (14.7 ± 1.8 vs. 14.8 ± 1.6 years, P = 0.9). There were non-significantly more males than females in GHD patients (59% vs. 50%, P = 0.7). Mean IGF-1 concentration was not significantly different (146.9 ± 70.4 ng/dl vs. 145.7 ± 69.8 ng/dl, P = 0.9). IGF-1 concentration below the reference ranges for age and gender was non-significantly higher in patients with GHD compared to non-GHD (53.8% vs. 46.2%, P = 0.8). The mean peak for GH concentration was significantly lower in patients with GHD (2.2 ± 1.3 ng/ml vs. 9.9 ± 5.6 ng/ml, P < 0.0001). Peak GH concentration was not significantly correlated with IGF-1 concentration (r = 0.213, P = 0.2). We plotted a ROC curve of IGF-1 concentration according to the diagnosis of GHD as established using ITT. The AUC was 49%. An IGF-1 threshold of 154 ng/dl was selected to emphasize sensitivity rather than specificity. With a threshold of 154 ng/dl, sensitivity was 52% (95% confidence interval (95% CI); 32%, 71%), specificity was 40% (95% CI; 19%, 64%) and the negative predictive value for the diagnosis of GHD was 38% (95% CI; 24%, 54%). With a threshold of 105 ng/dl, the sensitivity was 41% and the specificity was 70%. A threshold of 74 ng/dl, gave a positive predictive value of 60% but a negative predictive value of 43%. 7 of the patients with IGF-1 concentration above the threshold of 154 ng/dl (N = 20) were normal and 13 had GH deficiency. These 13 GHD patients had IGF-1 concentration that differs significantly from those of their GH-sufficient counterparts (105 ± 35 vs. 222 ± 49 ng/dl, P < 0.0001). If IGF-1 was used as a screening test (with a concentration threshold of 154 ng/dl) and ITT as a confirmatory test, 20 (43%) out of 47 ITT would not have been performed, leading to the misdiagnosis of 13 GH-deficient adults. Thus, in our study population, such a procedure would misdiagnose 13 out of 27 GHD patients (48%) and yield a sensitivity of 52%.
Conclusion: Many reports have already reported that IGF-1 concentration is lower in patients with GHD than in the general population, our study demonstrated the poor negative predictive value of IGF-1 concentration for the diagnosis of GHD, making it the need of the use of the “gold standard” method ITT. This observation remains to be validated by population-based studies.
Article DOI: 10.54178/jsedmv1i11994
Youngwanichsetha S. AGEs in diabetes prevention and management. Series Endo Diab Met. 2019;1(1):1- 2.
Article DOI: 10.54178/jsedmv1i11995
Ebe K, Bando H, Muneta T, et al. Evaluating insulin/glucose ratio using breakfast of calorie restriction meal for type 2 diabetes mellitus. Series Endo Diab Met. 2019;1(1):3-15.
Background: Type 2 diabetes mellitus (T2DM) has been a medical and social problem worldwide. For nutritional therapy, Low Carbohydrate Diet (LCD) and Calorie restriction (CR) have discussed for long, where authors continued clinical research.
Subjects and Methods: Subjects were 68 patients with T2DM with 62.1 years on average. Methods included i) standard CR was provided a day with 1400 kcal and 60% of carbohydrate, ii) measurement of daily profile of blood glucose, iii) insulinogenic index (IGI) (0-30 mins) exam for breakfast including 70g of carbohydrate, iv) calculation of IGI by delta and Area Under the Curves(AUC).
Results: Basal data revealed that HbA1c 7.9%, fasting glucose 163 mg/dL, average glucose in a day 210 mg/dL, M value 117 in the median. Increment of glucose/IRI was 48.0 mg/dL/8.6 μU/mL, respectively. Delta or AUC ratio of IGI was 0.14[0.08-0.26] and 3.3[2.5-5.2], respectively. There were significant correlations between M value and Delta or AUC ratio, with a higher coefficient in the latter.
Discussion and Conclusion: IGI study in Meal Tolerance Test (MTT) would be useful for pancreas function evaluation. AUC ratio method has superiority than Delta ratio with higher correlation coefficient. Current results could be the fundamental data for the related range of research, and further development will be expected.
Article DOI: 10.54178/jsedmv1i11996
