Factors associated with early relapse to insulin dependence in unprovoked A-β+ ketosis-prone diabetes

Abstract

Objective Unprovoked “A-β+” Ketosis-Prone Diabetes (KPD), a unique diabetic syndrome of adult-onset, obesity and proneness to ketoacidosis, is associated with rapid recovery of β cell function and insulin-independence. Whereas most patients experience prolonged remission, a subset relapses early to insulin dependence. We sought to define factors associated with early relapse. Methods We utilized a prospective, longitudinal database to analyze 50 unprovoked A-β+ KPD patients with ≥2 measurements of β cell function and glycemia following baseline assessment. Results 19 patients (38%) relapsed to insulin dependence <1y after the index DKA episode, while 31 (62%) remained insulin-independent for >1y (median 4.2y). Younger age at baseline (OR=0.947, P=0.033), and lower HOMA2-%β (OR=0.982, P=0.001), lower HOMA2-IR (OR=0.582, P=0.046) and higher HbA1c at 1y (OR=1.71, P=0.002) were associated with early relapse. A multivariate model with these variables and the interaction of HOMA2-%β and HbA1c at 1y provided a good fit (P<0.05). Conclusions Relapse to insulin dependence in unprovoked A-β+ KPD patients is associated with younger age and, after 1y, lack of robust increase in β cell functional reserve, and suboptimal glycemic control. Measurements of these parameters 1y after the index DKA episode can be used to assess the need for insulin therapy.

Protective Effect of Camel Milk as Anti-Diabetic Supplement: Biochemical, Molecular and Immunohistochemical Study

“…Only 5%-10% of diabetic patients do not produce insulin because of complete destruction in pancreatic β-cells that results in hyperglycemia and ketoacidosis in type-1 diabetic patients (Gaba et al 2015). Type 2 diabetes (T2D), a non-insulin-dependent diabetes mellitus, is associated with insulin resistance as cells of the body can't respond to insulin.…”

Advancing clinical care for the patients with ketosis-prone diabetes: from knowledge to action

“…Recently, studies in drug-naïve subjects with newly diagnosed type 2 diabetes unequivocally showed that initiation of triple hypoglycemic therapy with metformin, pioglitazone and glyburide (Lingvay, Legendre, Kaloyanova, et al, 2009) or exenatide (Abdul-Ghani, Puckett, Triplitt, et al, 2015 will maintain A1C below 6.5% and be safe when prescribed for 3 years. What Gaba et al (2015) also emphasized in their report is that β-cell reserve is diminished by 2-fold in "A − β+" KPD patients who relapsed during the first year of remission. Therefore, another strategy to mitigate risk of relapse could include early and continuous use of insulin therapy even during time of remission.…”

“…In keeping with this most sacred physician duty, the report by Gaba et al (2015) widens our horizons in helping us to deliver better care for KPD patients. The authors broaden our knowledge of KPD pathophysiology, but the results of this and other studies also do emphasize that there are too many who will relapse.…”

“…The study by Gaba et al (2015) has several limitations. It was conducted in the single tertiary care center; the choice of oral hypoglycemic agents between 1999 and 2012 was likely changing with the appearance on the market of newer anti-diabetic therapies in late 2000s; and not all clinic patients with KPD had comprehensive metabolic assessment during follow up which limited number of subjects studied.…”

“…In this issue of the Journal Gaba, Gambhire, Uy, et al (2015), embraced this task of advancing our knowledge in understanding risk factors that could signal KPD recurrence. The authors noted that, since the initiation of systematic standardized care for KPD patients in their dedicated clinic, 38% of unprovoked, i.e., no evident provoking factor(s) was identified precipitating index DKA, "A − β+" KPD patients relapsed to insulin requirement within 1 year after index DKA episode despite routine prescription of diet and oral hypoglycemic agents.…”