The Effects of DPP IV Inhibitor on Glycemic Variability in Type 2 Diabetic Patients Treated with Twice Daily Premixed Human Insulin

Glycemic variability (GV) is emerging as an exciting therapeutic target for diabetes mellitus (DM) with recent evidences showing association of GV with hypoglycemia risk as well as chronic complications.(1,2) Twice daily human premixed insulin is commonly used in developing countries and Asia for treatment of type 2 DM (T2DM). (3) Downloaded from https://academic.oup.com/jes/article/4/Supplement_1/MON-653/5833510 by UNIVERSITI MALAYSIA SARAWAK user on 09 September 2020 doi: 10.1210/jendso/bvaa046 | Journal of the Endocrine Society | A397 A397 JESOCI, Volume 4, Abstract Supplement, 2020 While more convenient and cost saving, human premixed insulin regime may increase GV due to lesser flexibility and less physiological pharmacokinetic profile. Dipeptidyl peptidase IV inhibitors (DPPIV-I) have been shown to improve GV when used for treatment of T2DM but the effects of DPPIV-I when added on human premixed insulin is limited. We therefore evaluated the changes in GV following addition of DPP IV-I among T2DM patients treated with premixed human insulin with or without metformin therapy. This was a prospective study involving adult patients with T2DM on stable doses of premixed human insulin with or without metformin for at least 3 months from two state hospitals in Malaysia. Blinded continuous glucose monitoring (CGM) were performed at baseline and following 6 weeks of adding Vildagliptin to their insulin regime. A total of 12 patients were recruited (50% male). Mean (SD) age was 55.8 (13) years with mean duration of disease of 14 (6.6) years. The addition of Vildagliptin significantly reduced GV indexes including SD 2.98 (1.17) to 2.33 (0.82), p=0.017; MAGE 6.94 (2.61) to 5.72 (1.87), p=0.018; MAG 1.60 (0.76) to 1.23 (0.48), p=0.009 and M Value 13.96 (13.01) to 6.52 (7.45), p=0.037. In addition there were improvements in terms of parameters for glycemic control. Time spent in optimal glycemic range (4-8 mmol/l) improved from 38.33 (19.69) to 58.17 (5.95) %, p=0.001 with reduction in AUC for hyperglycemia from 2.09 (1.73) to 1.06 (1.09) mmol/day, p=0.010. Hypoglycemia events were infrequent and the reduction in time spent in hypoglycemia [5.92(9.74) to 1.91 (2.54)%, p=0.191] as well as AUC for hypoglycemia [0.03(0.54) to 0.01(0.02) mmol/day, p=0.163] were found although these did not reach statistical significance. We concluded that addition of DPP IV-I to commonly prescribed twice daily premixed human insulin regime in patients with T2DM may improve GV and glycemic control and warrant further exploratio

The Effects of DPP IV Inhibitor on Glycemic Variability in Type 2 Diabetic Patients Treated with Twice Daily Premixed Human Insulin

Glycemic variability (GV) is emerging as an exciting therapeutic target for diabetes mellitus (DM) with recent evidences showing association of GV with hypoglycemia risk as well as chronic complications.(1,2) Twice daily human premixed insulin is commonly used in developing countries and Asia for treatment of type 2 DM (T2DM). (3) While more convenient and cost saving, human premixed insulin regime may increase GV due to lesser flexibility and less physiological pharmacokinetic profile. Dipeptidyl peptidase IV inhibitors (DPPIV-I) have been shown to improve GV when used for treatment of T2DM but the effects of DPPIV-I when added on human premixed insulin is limited. We therefore evaluated the changes in GV following addition of DPP IV-I among T2DM patients treated with premixed human insulin with or without metformin therapy. This was a prospective study involving adult patients with T2DM on stable doses of premixed human insulin with or without metformin for at least 3 months from two state hospitals in Malaysia. Blinded continuous glucose monitoring (CGM) were performed at baseline and following 6 weeks of adding Vildagliptin to their insulin regime. A total of 12 patients were recruited (50% male). Mean (SD) age was 55.8 (13) years with mean duration of disease of 14 (6.6) years. The addition of Vildagliptin significantly reduced GV indexes including SD 2.98 (1.17) to 2.33 (0.82), p=0.017; MAGE 6.94 (2.61) to 5.72 (1.87), p=0.018; MAG 1.60 (0.76) to 1.23 (0.48), p=0.009 and M Value 13.96 (13.01) to 6.52 (7.45), p=0.037. In addition there were improvements in terms of parameters for glycemic control. Time spent in optimal glycemic range (4-8 mmol/l) improved from 38.33 (19.69) to 58.17 (5.95) %, p=0.001 with reduction in AUC for hyperglycemia from 2.09 (1.73) to 1.06 (1.09) mmol/day, p=0.010. Hypoglycemia events were infrequent and the reduction in time spent in hypoglycemia [5.92(9.74) to 1.91 (2.54)%, p=0.191] as well as AUC for hypoglycemia [0.03(0.54) to 0.01(0.02) mmol/day, p=0.163] were found although these did not reach statistical significance. We concluded that addition of DPP IV-I to commonly prescribed twice daily premixed human insulin regime in patients with T2DM may improve GV and glycemic control and warrant further exploration

The effect of DPP4 Inhibitor on glycemic variability in patients with type 2 diabetes treated with twice daily premixed human insulin

Objective. To evaluate the effect of adding DPP4 inhibitor (DPP4-i) on glycemic variability (GV) in patients with type 2 diabetes mellitus (T2DM) treated with premixed human insulin (MHI). Methodology. We conducted a prospective study in patients with T2DM on twice-daily MHI with or without metformin therapy. Blinded continuous glucose monitoring was performed at baseline and following 6 weeks of Vildagliptin therapy. Results. Twelve patients with mean (SD) age of 55.8 (13.1) years and duration of disease of 14.0 (6.6) years were recruited. The addition of Vildagliptin significantly reduced GV indices (mmol/L): SD from 2.73 (IQR 2.12-3.66) to 2.11 (1.76-2.55), p=0.015; mean amplitude of glycemic excursions (MAGE) 6.94(2.61) to 5.72 (1.87), p=0.018 and CV 34.05 (8.76) to 28.19 (5.36), p=0.010. In addition, % time in range (3.9-10 mmol/l) improved from 61.17 (20.50) to 79.67 (15.33)%, p=0.001; % time above range reduced from 32.92 (23.99) to 18.50 (15.62)%, p=0.016; with reduction in AUC for hyperglycemia from 1.24 (1.31) to 0.47 (0.71) mmol/day, p=0.015. Hypoglycemic events were infrequent and the reduction in time below range and AUC for hypoglycemia did not reach statistical significance. Conclusion. The addition of DPP4-I to commonly prescribed twice-daily MHI in patients with T2DM improves GV and warrants further exploration

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case–control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BC(OG)) and IVGTT (BC(IV)), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUC(GLP-1)). Per cent incretin effect was estimated as 100×(BC(OG)−BC(IV))/BC(OG)). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BC(OG), p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUC(GLP-1) but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254

Co-Occurrence of Exogenous and Endogenous Cushing’s Syndromes—Dilemma in Diagnosis

Approach to patients who manifest with features of Cushing’s syndrome often begin with exclusion of exposure to excessive exogenous source of glucocorticoids (GC). Most guidelines advocate no further assessment if excessive exogenous GC use is present. We present a case of a 66-year-old lady who was noted to have typical features of Cushing’s syndrome. As she gave a very clear history of ingesting exogenous GC for a year, no further work up was undertaken. Despite cessation of GC for a year, she continued to have thin skin and easy bruising. Upon admission for hypertensive emergency, her clinician took note of her changes and investigated her for endogenous Cushing’s syndrome. Her cortisol post overnight dexamethasone suppression test was 707 nmol/l. Post low dose dexamethasone suppression test yielded a cortisol of 1133.2 nmol/l. 24 hours urine cortisol was 432.2 nmol/l. Plasma ACTH was 1.1 pmol/l, indicating an ACTH independent Cushing’s syndrome. We proceeded with Computed tomography scan (CT scan) of adrenals which revealed a right adrenal adenoma measuring 4.4 × 3.4 × 4.0 cm. Right retroperiteneoscopic adrenalectomy was done. Histopathology examination was consistent with adrenal cortical adenoma with foci of myelolipoma. Post adrenalectomy she developed hypocortisolism secondary to contralateral adrenal suppression which lasted up to the present date. Her cutaneous and musculoskeletal manifestations improved substantially. Co-occurrence of endogenous and exogenous Cushing’s syndromes is uncommon but should be considered in patients whose Cushingnoid features do not resolve after cessation of exogenous GC

International multicenter survey on screening and confirmatory testing in primary aldosteronism

OBJECTIVE Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA

International multicenter survey on screening and confirmatory testing in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA