PMID- 10443650
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 8
DP  - 1999 Aug
TI  - Progressive decline in insulin levels in Rabson-Mendenhall syndrome.
PG  - 2623-9
AB  - Mutations in the insulin receptor gene cause the severe insulin-resistant
      syndromes leprechaunism and Rabson-Mendenhall syndrome, whose metabolic features 
      include fasting hypoglycemia, post-prandial hyperglycemia, and extremely elevated
      insulin levels. Patients with Rabson-Mendenhall syndrome have a protracted course
      and eventually develop ketoacidosis. To determine the mechanism causing this
      progression and the paradoxical fasting hypoglycemia, we conducted a
      retrospective study in a patient with Rabson-Mendenhall syndrome, who was a
      compound heterozygous for two missense mutations affecting the kinase domain of
      the insulin receptor beta-subunit (I1115T and R1131W). At birth, the patient had 
      fasting hypoglycemia and postprandial hyperglycemia. This was followed at
      approximately 3 yr of age by constant hyperglycemia and, at 6 yr of age, by
      constant ketoacidosis. Urinary organic acids during ketoacidosis resembled those 
      of patients with type 1 diabetes. Plasma glucose levels increased (r2 = 0.31; P <
      0.01), whereas insulin levels decreased with age (r2 = 0.51; P < 0.01). During
      periods ofhypoglycemia and hyperglycemia (0-1 yr of age), constant hyperglycemia 
      (3-4 yr of age), and hyperglycemia with ketoacidosis (6-7 yr of age), insulin
      levels were significantly correlated with plasma glucose levels (P < 0.05).
      However, the slope of the regression and the predicted insulin level at zero
      glucose decreased with increasing age. When insulin levels were normalized for
      the plasma glucose concentrations, an exponential decrease in the insulin/glucose
      ratio was observed (r2 = 0.92; P < 0.01), with most of the decline occurring
      before 2 yr of age. These results indicate that the paradoxical fasting
      hypoglycemia of patients with Rabson-Mendenhall syndrome is associated with
      severely increased levels of circulating insulin and that the progression of this
      disease is due to a decline in insulin levels.
FAU - Longo, N
AU  - Longo N
AD  - Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA.
FAU - Wang, Y
AU  - Wang Y
FAU - Pasquali, M
AU  - Pasquali M
LA  - eng
GR  - DK-48742/DK/NIDDK NIH HHS/United States
GR  - M01-RR-00039/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Phosphoproteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Blood Glucose/analysis
MH  - Child
MH  - Diabetic Ketoacidosis/etiology
MH  - Humans
MH  - Insulin/*blood
MH  - Insulin Receptor Substrate Proteins
MH  - *Insulin Resistance
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Male
MH  - *Mutation
MH  - Phosphoproteins/genetics
MH  - Receptor, Insulin/*genetics
MH  - Syndrome
EDAT- 1999/08/12 00:00
MHDA- 1999/08/12 00:01
CRDT- 1999/08/12 00:00
PHST- 1999/08/12 00:00 [pubmed]
PHST- 1999/08/12 00:01 [medline]
PHST- 1999/08/12 00:00 [entrez]
AID - 10.1210/jcem.84.8.5902 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Aug;84(8):2623-9. doi: 10.1210/jcem.84.8.5902.