title: Urinary C-peptide creatinine ratio detects absolute insulin deficiency in Type 2 diabetes.
abstract: OBJECTIVE
  To determine the prevalence and clinical characteristics of absolute insulin deficiency in long-standing Type 2 diabetes, using a strategy based on home urinary C-peptide creatinine ratio measurement.
  
  
  METHODS
  We assessed the urinary C-peptide creatinine ratios, from urine samples taken at home 2 h after the largest meal of the day, in 191 insulin-treated subjects with Type 2 diabetes (diagnosis age ≥45 years, no insulin in the first year). If the initial urinary C-peptide creatinine ratio was ≤0.2 nmol/mmol (representing absolute insulin deficiency), the assessment was repeated. A standardized mixed-meal tolerance test with 90-min stimulated serum C-peptide measurement was performed in nine subjects with a urinary C-peptide creatinine ratio ≤ 0.2 nmol/mmol (and in nine controls with a urinary C-peptide creatinine ratio >0.2 nmol/mmol) to confirm absolute insulin deficiency.
  
  
  RESULTS
  A total of 2.7% of participants had absolute insulin deficiency confirmed by a mixed-meal tolerance test. They were identified initially using urinary C-peptide creatinine ratio: 11/191 subjects (5.8%) had two consistent urinary C-peptide creatinine ratios ≤ 0.2 nmol/mmol; 9 of these 11 subjects completed a mixed-meal tolerance test and had a median stimulated serum C-peptide of 0.18 nmol/l. Five of these 9 had stimulated serum C-peptide <0.2 nmol/l and 9/9 subjects with urinary C-peptide creatinine ratio >0.2 had endogenous insulin secretion confirmed by the mixed-meal tolerance test. Compared with subjects with a urinary C-peptide creatinine ratio >0.2 nmol/mmol, those with confirmed absolute insulin deficiency had a shorter time to insulin treatment (median 2.5 vs. 6 years, P=0.005) and lower BMI (25.1 vs. 29.1 kg/m(2) , P=0.04). Two out of the five patients with absolute insulin deficiency were glutamic acid decarboxylase autoantibody-positive.
  
  
  CONCLUSIONS
  Absolute insulin deficiency may occur in long-standing Type 2 diabetes, and cannot be reliably predicted by clinical features or autoantibodies. Absolute insulin deficiency in Type 2 diabetes may increase the risk of hypoglycaemia and ketoacidosis, as in Type 1 diabetes. Its recognition should help guide treatment, education and management. The urinary C-peptide creatinine ratio is a practical non-invasive method to aid detection of absolute insulin deficiency, with a urinary C-peptide creatinine ratio > 0.2 nmol/mmol being a reliable indicator of retained endogenous insulin secretion.
authors: Department of Geriatrics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; NIHR Exeter Clinical Research Facility, Exeter, UK.
authors: S V
authors: SV
authors: Hope
authors: A G
authors: AG
authors: Jones
authors: E
authors: E
authors: Goodchild
authors: M
authors: M
authors: Shepherd
authors: R E J
authors: RE
authors: Besser
authors: B
authors: B
authors: Shields
authors: T
authors: T
authors: McDonald
authors: B A
authors: BA
authors: Knight
authors: A
authors: A
authors: Hattersley
mesh_terms: D000368:Aged; D002096:C-Peptide / Q000096:biosynthesis* / Q000652:urine*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D005260:Female; D006801:Humans; D007328:Insulin / Q000172:deficiency*; D008297:Male; D008875:Middle Aged
chemical_list: D002096:C-Peptide; D007328:Insulin; D003404:Creatinine
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