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© 2004 by the American Diabetes Association, Inc.
Letters: Observations |
Remitting Diabetes
A new genetic subgroup?
1 National Health Service Trust, Epsom and St. Helier University Hospitals, Queen Mary’s Hospital for Children, Epsom and St. Helier University Hospitals National Health Service Trust, Carshalton, Surrey, U.K
2 Department of Diabetes, School of Postgraduate Medicine, Royal Devon and Exeter, National Health Service Healthcare Trust, Exeter, U.K
Address correspondence to Dr. Christine P. Burren, Queen Mary’s Hospital for Children, St. Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA, U.K. E-mail:christine{at}cpburren.freeserve.co.uk
We describe a previously unreported clinical scenario of remitting diabetes in two young brothers who do not fit existing diagnostic classifications. They may represent a new genetic subgroup of diabetes.
Case 1 presented at 3.6 years with poor linear growth, polyuria, and polydipsia. Diabetes was diagnosed based on a blood glucose value of 11.5 mmol/l and an elevated HbA1c of 7.0% (normal 3.8–6.0). During 3 months’ observation, hyperglycemia and an elevated HbA1c persisted. Working diagnosis was very early type 1 diabetes, and insulin was commenced (0.2 units · kg–1 · day–1). HbA1c improved from 7.0 to 5.3%. However, linear growth did not improve.
The family also tested asymptomatic siblings and identified hyperglycemia in the 18-month-old brother. Diabetes was diagnosed on repeated blood glucose values >11 mmol/l and HbA1c 9.0%. Although thriving, there was concern of early type 1 diabetes, and he commenced insulin (0.2 units · kg–1 · day–1). HbA1c normalized to 5.5% after 16 months. Two additional family members had glucose abnormalities: the 44-year-old father had impaired glucose tolerance (IGT) (glucose 6.4 mmol/l [0 min] and 10.4 mmol/l [120 min] in an oral glucose tolerance test [OGTT]; BMI 29 kg/m2), and the 74-year-old paternal grandmother was diagnosed with type 2 diabetes at age 60 years and is on metformin (not overweight, no diabetes complications). The mother’s OGTT was normal.
No evidence of autoimmunity was found in either child (insulin, islet cell, and GAD antibodies). After age 1.6 and 2.3 years, respectively, insulin was ceased, as requirements had remained low with normal HbA1c and blood glucose. Both boys had OGTTs showing normal glucose tolerance. Interestingly, the older boy had hypoglycemia (glucose 2.0 mmol/l) at 120 min of OGTT, suggesting possible insulin secretion dysregulation. After 2 years off insulin, HbA1c has remained normal (5.4–5.5%).
The cause of diabetes resolution in these boys remains unexplained. Transient hyperglycemia can occur during intercurrent illness, is of very short duration, and is not associated with elevated HbA1c. Although type 1 diabetes was the initial diagnosis, their subsequent clinical course and absence of autoimmunity markers make this unlikely. Type 1 diabetes may have an extended honeymoon (i.e., partial remission), sometimes up to 2 years, but normal HbA1c off treatment 4 years after diagnosis is very unusual. IGT in the father and type 2 diabetes in the paternal grandmother is consistent with autosomal-dominant inheritance suggesting maturity-onset diabetes of the young (MODY); however, no MODY subgroups remit (1). While glucokinase mutations could explain the adults’ hyperglycemia, neither child had fasting blood glucose (>5 mmol/l) effectively excluding MODY2. Case 1 tested negative for hepatocyte nuclear factor-
(HNF-1) mutations. Transient neonatal diabetes remits but is excluded as they presented after age 3 months (1.5 and 3.6 years). A remitting form of atypical diabetes is described in black adolescent Americans (2) but not in whites or young children.
In summary, disappearance of diabetes in these young boys is unusual and does not fit clinically recognized syndromes. Two affected siblings suggest a novel genetic syndrome probably altering ß-cell function. This could be a recessive condition with coincidental hyperglycemia in adults. Alternatively, it may represent different stages in a dominant disorder, with adults having undetected hyperglycemia during childhood, suggesting that the children may later relapse. This cyclical pattern of diabetes remission and relapse occurs in transient neonatal diabetes, and we hypothesize a novel genetic mutation causing a similar process. We would welcome reports of further cases of remitting diabetes, as they could provide further insights into this potential new genetic form of diabetes.
References
- Stride A, Hattersley AT: Different genes, different diabetes. Annal Med 34:207–216, 2002
- Winter WE, Maclaren NK, Riley WJ, Clarke DW, Kappy MS, Spillar RP: Maturity-onset diabetes of youth in black Americans. N Engl J Med 316:285–291, 1987[Abstract]
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