Urine C-Peptide Creatinine Ratio Is a Noninvasive Alternative to the Mixed-Meal Tolerance Test in Children and Adults With Type 1 Diabetes

Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, UK.
Diabetes care (Impact Factor: 8.42). 02/2011; 34(3):607-9. DOI: 10.2337/dc10-2114
Source: PubMed

ABSTRACT Stimulated serum C-peptide (sCP) during a mixed-meal tolerance test (MMTT) is the gold standard measure of endogenous insulin secretion, but practical issues limit its use. We assessed urine C-peptide creatinine ratio (UCPCR) as an alternative.
Seventy-two type 1 diabetic patients (age of diagnosis median 14 years [interquartile range 10-22]; diabetes duration 6.5 [2.3-32.7]) had an MMTT. sCP was collected at 90 min. Urine for UCPCR was collected at 120 min and following a home evening meal.
MMTT 120-min UCPCR was highly correlated to 90-min sCP (r = 0.97; P < 0.0001). UCPCR ≥ 0.53 nmol/mmol had 94% sensitivity/100% specificity for significant endogenous insulin secretion (90-min sCP ≥ 0.2 nmol/L). The 120-min postprandial evening meal UCPCR was highly correlated to 90-min sCP (r = 0.91; P < 0.0001). UCPCR ≥ 0.37 nmol/mmol had 84% sensitivity/97% specificity for sCP ≥ 0.2 nmol/L.
UCPCR testing is a sensitive and specific method for detecting insulin secretion. UCPCR may be a practical alternative to serum C-peptide testing, avoiding the need for inpatient investigation.

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Available from: Johnny Ludvigsson, Sep 28, 2015
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    • "The urine sample was collected in a standard mid‐stream urine boric acid‐containing specimen pot, and returned by post to the routine pathology laboratories for UCPCR analysis. UCPCR ≤ 0.2 nmol/mmol is equivalent to a stimulated serum C‐peptide (sSCP) of 0.2 nmol/l in an MMTT 15, representing an absence of clinically significant insulin secretion 11. This level is associated with unstable glycaemia, increased risk of hypoglycaemia and microvascular complications (as well as absolute insulin requirement) in Type 1 diabetes 11. "
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    ABSTRACT: Aims 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/m2, 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.
    Diabetic Medicine 05/2013; DOI:10.1111/dme.12222 · 3.12 Impact Factor
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    • "We recruited 102 adults with insulin treated diabetes, HbA1c <86 mmol/mol (10%) and without renal impairment (eGFR > 60mls/min/1.73 m2) from existing research databases and clinical secondary care, as described previously [24,25]. 58 had Type 1 diabetes (16 within 3 years of diagnosis, median (interquartile range, IQR) age of diagnosis 20 (14–27), BMI 25 (22–27)), 44 had Type 2 diabetes (median (IQR) age of diagnosis 55 (47–59), BMI 29(28–36), classification based on clinical diagnosis from health records), 60 were male. "
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    ABSTRACT: In patients with both Type 1 and Type 2 diabetes endogenous insulin secretion falls with time which changes treatment requirements, however direct measurement of endogenous insulin secretion is rarely performed. We aimed to assess the impact of endogenous insulin secretion on postprandial glucose increase and the effectiveness of prandial exogenous insulin. We assessed endogenous insulin secretion in 102 participants with insulin treated diabetes (58 Type 1) following a standardised mixed meal without exogenous insulin. We tested the relationship between endogenous insulin secretion and post meal hyperglycaemia. In 80 participants treated with fast acting breakfast insulin we repeated the mixed meal with participants' usual insulin given and assessed the impact of endogenous insulin secretion on response to exogenous prandial insulin. Post meal glucose increment (90 minute - fasting) was inversely correlated with endogenous insulin secretion (90 minute C-peptide) (Spearman's r = -0.70, p < 0.001). Similar doses of exogenous prandial insulin lowered glucose increment more when patients had less endogenous insulin; by 6.4(4.2-11.1) verses 1.2(0.03-2.88) mmol/L (p < 0.001) for patients in the lowest verses highest tertiles of endogenous insulin. In insulin treated patients the measurement of endogenous insulin secretion may help predict the degree of postprandial hyperglycaemia and the likely response to prandial insulin.
    BMC Endocrine Disorders 06/2012; 12(1):6. DOI:10.1186/1472-6823-12-6 · 1.71 Impact Factor
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    • "Therefore, the detection of C-peptide outside the honeymoon period should raise the possibility of a diagnosis of MODY [Hattersley et al., 2006]. Random serum C-peptide testing at diagnosis can help with diabetes classification in children and adolescents [Ludvigsson et al., 2012], urine C-peptide is a noninvasive alternative test that circumvents the practical limitations of blood testing but gives equivalent results [Besser et al., 2011a]. A urinary C-peptide/creatinine ratio) cutoff of ≥ 0.2 nmol/mmol was able to discriminate HNF1A/4A MODY from type 1 diabetes with 97% sensitivity and 96% specificity [Besser et al., 2011b]. "
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    ABSTRACT: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset (often <25 years of age), and pancreatic beta-cell dysfunction. MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. A total of 193 different mutations have been described in 373 families. The most common mutation is Pro291fs (P291fsinsC) in the polycytosine (poly C) tract of exon 4, which has been reported in 65 families. HNF4A mutations are rarer; 31 mutations reported in 40 families. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management.
    Human Mutation 09/2006; 27(9):854-69. DOI:10.1002/humu.20357 · 5.14 Impact Factor
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