Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

Abstract

Aims/hypothesis The aim of the present study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes, a novel subtype of type 1B diabetes. Materials and methods In a nationwide survey, we followed 41 patients with fulminant type 1 diabetes and 76 age-and sex-matched patients with type 1A diabetes for 5 years. The following data were recorded every 12 months after the onset of diabetes: seven-point blood glucose concentrations, HbA 1c level, urinary albumin excretion, serum C-peptide level, blood pressure, daily dosages of insulin, frequency of severe hypoglycaemic episodes, and neurological and fundoscopic examination. ResultsThe 5-year cumulative incidence of microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A diabetes. In longitudinal studies using the KaplanMeier method, the cumulative incidence of each form of microangiopathy was significantly higher in fulminant type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0% (p=0.014), nephropathy 12.2% vs 2.6% (p=0.015) and neuropathy 12.2% vs 1.3% (p=0.010), respectively. Mean HbA 1c levels were similar in the fulminant and type 1A diabetes groups during the follow-up periods. However, the mean M-value, mean insulin dosages and the frequency of severe hypoglycaemic episodes were significantly higher, and the mean postprandial C-peptide level was significantly lower in the fulminant type 1 diabetes group.

Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes

“…The deviation index (δ) of each individual glucose value (γ) is first calculated as δ = (10 × log[γ/5.0]) 3 . M ‐value is the average of all the individually calculated deviation indices (∑δ/ n ) 6 .…”

High risk of renal dysfunction in patients with fulminant type 1 diabetes

“…A diagnosis of fulminant type 1 diabetes was made based on the following criteria2: ketosis or ketoacidosis for approximately 1 week after diabetes onset, blood glucose levels >288 mg/dL, glycated hemoglobin (HbA 1c ) levels <8.5% at the initial visit, urine C‐peptide <10 μg/day at the time of onset and fasting serum C‐peptide <0.3 ng/mL or serum C‐peptide <0.5 ng/mL after glucagon loading (or 2 h after a meal). Acute‐onset type 1 diabetes was defined as follows6: the presence of ketoacidosis or ketosis at diabetes onset, hyperglycemic symptoms within the 3 months preceding initiation of insulin therapy, requiring insulin therapy after diabetes onset and the presence of at least one islet‐related autoantibody (e.g., glutamic acid decarboxylase antibodies, insulin antibodies, anti‐insulinoma‐associated antigen 2 antibodies, zinc transporter 8 antibodies). Patients with estimated GFR <60 mL/min/1.73 m 2 at the time of diabetes onset were excluded.…”

“…The primary outcome of the present study was the incidence of renal dysfunction, defined as the first time when estimated GFR levels were <60 mL/min/1.73 m 2 8. The secondary outcome was the incidence of microalbuminuria, defined as the first time when urinary albumin excretion was ≥30 mg/g creatinine in the absence of urinary tract infection and/or hematuria6. Dyslipidemia was defined as follows: triglycerides ≥150 mg/dL, high‐density lipoprotein cholesterol <40 mg/dL, low‐density lipoprotein cholesterol ≥140 mg/dL (calculated using the Friedewald formula9), previous diagnosis of dyslipidemia or currently undergoing treatment with antidyslipidemic medications.…”

“…A previous study reported that patients with fulminant type 1 diabetes were at a higher risk of developing microalbuminuria than those with acute‐onset type 1 diabetes6, whereas another report showed that this risk did not differ between patients with fulminant type 1 diabetes and those with acute‐onset type 1 diabetes7. However, currently, there are no studies that compare the risk of developing renal dysfunction in these patients.…”

Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes [Review]

“…Due to rushed clinical course in most cases, patients with fulminant type 1 diabetes sometimes remain untreated until becoming comatose and/or entering a critical, life-threatening state [4]. Endogenous insulin secretion is completely abolished over time and diabetic microangiopathies develop within a short duration [5,6]. Remarkable severe insulitis was recognized in autopsied pancreata of patients who died shortly after the onset of fulminant type 1 diabetes [3,[7][8][9][10].…”