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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 12 6331-6335
Copyright © 2004 by The Endocrine Society

Improved Glycemic Control in Subjects with Atypical Diabetes Results from Restored Insulin Secretion, But Not Improved Insulin Sensitivity

Neda Rasouli and Steven C. Elbein

University of Arkansas for Medical Sciences, and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205

Address all correspondence and requests for reprints to: Dr. Neda Rasouli, Central Arkansas Veteran Health, 4300 West 7th Street, 111J, Little Rock, Arkansas 72205. E-mail: rasoulineda{at}uams.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
African-American subjects often present with hyperglycemic crisis (diabetic ketoacidosis or severe hyperglycemia), yet subsequently are treated without insulin. The pathophysiology of this unique condition is unknown. We hypothesized that recovery from atypical diabetes with intensive insulin therapy resulted from a reversal of a defect in ß-cell function and improved insulin sensitivity. We studied eight newly diagnosed, antibody-negative African-American subjects (age, 34–56 yr) who presented with hyperglycemic crisis. Subjects were studied at baseline after overnight glycemic control and again after 3 wk and 3 months of intensive insulin therapy. Insulin sensitivity (SI) was determined from an insulin-modified, frequently sampled iv glucose tolerance test, and insulin secretion was measured as the acute insulin response to glucose and to a glucagon stimulation test. Fructosamine and hemoglobin A1c declined significantly with intensive insulin therapy, and insulin requirements decreased over time. Both acute insulin response to glucose and the C peptide response to glucagon stimulation test improved by 3 wk (P = 0.02 vs. baseline), and improvements were maintained at 3 months (P = 0.02 vs. baseline). In contrast, the SI remained low throughout the study. We demonstrate that improved glycemic control correlates with a remarkable recovery of ß-cell function, but no change in SI.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ATYPICAL DIABETES (Flatbush diabetes) was originally described by Banerji et al. (1) as a unique form of diabetes among African-American patients who presented with diabetic ketoacidosis (DKA) as the initial manifestation of diabetes, but whose subsequent clinical course resembled typical type 2 diabetes mellitus (T2DM). These patients are usually obese, have no markers of autoimmune ß-cell failure [glutamic acid decarboxylase (GAD) antibody], and have no identified precipitating cause of DKA (1, 2). This atypical presentation has been also reported in other ethnicities (3, 4) and has been called by various names, including idiopathic T1DM (5) and ketosis-prone diabetes B+A– (6, 7). This group of patients appears to differ from those with typical T2DM in that normoglycemic remission may occur without weight loss (8, 9, 10). The long-term insulin independence distinguishes atypical diabetes from T1DM, in which subjects are usually lean and have a high incidence of detectable autoimmunity (11).

The pathophysiology of the ketoacidosis in atypical diabetes and the mechanism of the subsequent recovery are unknown. The prevention of a recurrence of hyperglycemia by low dose sulfonylurea treatment (8, 10) suggests a recovery of ß-cell function. Because a prospective study to determine the events before the onset of atypical diabetes is impossible, we used intensive insulin therapy to rapidly improve glycemic control. We then followed the insulin sensitivity and ß-cell function from immediately after resolution of the hyperglycemic crisis through the first 3 months of treatment. We hypothesized that recovery from atypical diabetes resulted from a restoration of ß-cell function and improved insulin sensitivity.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Experimental subjects

The study was performed in General Clinical Research Clinic (GCRC), and the study design was approved by the University of Arkansas for Medical Sciences institutional research board. All subjects provided written informed consent before entering the research study.

Participants were African-American patients who presented with hyperglycemic crisis, defined as symptomatic hyperglycemia with a plasma glucose level over 30 mmol/liter (540 mg/dl) or hyperglycemia with ketosis (serum ketone, ≥2+) as a first manifestation of diabetes without other known precipitating factors, such as sepsis or myocardial infarction. All subjects were GAD antibody negative, and all but one subject had a baseline evaluation performed within 1 wk of hospital admission for DKA or severe hyperglycemia.

Study design

Subjects were admitted to the GCRC on the night before the study. A variable insulin infusion was given overnight to bring the glucose to approximately 6 mmol/liter (110 mg/dl). On the first visit, subjects had height measured by a wall-mounted stadiometer, and weight determined by an electronic balance. Body composition was measured by dual x-ray absorptiometry. Subjects then underwent an insulin-modified frequently sampled iv glucose tolerance test (FSIGT) in the fasting state, followed by a glucagon stimulation test (GST), as described below. During the FSIGT, subjects received 11.4 g/m2 glucose at baseline, and samples were collected at 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 19 min. At 20 min, regular insulin (0.04 U/kg) was infused iv over 30 sec, and sampling was continued at 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180 min for glucose and insulin measurements. An additional sample was obtained at 240 min if the glucose level had not returned to baseline. At the conclusion of the FSIGT, when the glucose level returned to baseline (180–240 min), subjects received 1 mg glucagon, iv, and samples were obtained at 0, 3, 6, 10, and 20 min for measurement of glucose and C peptide levels (GST). Subjects were then placed on an intensive conventional insulin therapy (regular insulin before each meal and NPH insulin at bedtime). Subjects were instructed to monitor and record their capillary glucose before each meal and at bedtime as well as with any hypoglycemic symptoms. Subjects were readmitted after 3 wk and again after 3 months of intensive treatment, but had phone contact with the study investigators and diabetes educators twice weekly for the first 3 wk and then every other week for the remainder of the study. Glucose control was evaluated by a continuous glucose monitoring system (Medtronic MiniMed, Inc., Northridge, CA) after 4–6 wk of intensive insulin treatment, and insulin dosage was adjusted based on the results. Subjects did not receive any oral agents for glycemic control during the study.

Laboratory procedures

Insulin and C peptide levels were measured by an immunochemiluminometric assay (MLT Assay, Wales, UK) in the GCRC Core Laboratory. The sensitivity was 0.25 mU/liter for insulin with 1% cross-reactivity with proinsulin and a 4–8% coefficient of variation, and C peptide sensitivity was 5 pmol/liter with 2% cross-reactivity with proinsulin and a 6–7% coefficient of variation. Plasma glucose was measured by a glucose oxidase assay, hemoglobin A1c (HbA1c) was measured by immunoassay (normal range, 4.5–5.7%), and fructosamine levels (normal range, 0–285 µmol/liter) were measured by colorimetric method (0–285 µmol/liter), both performed by LabCorp, Inc. (Burlington, NC).

Statistical methods

Data are expressed as the mean ± SD. Differences were considered significant at P < 0.05. Continuous variables were compared between baseline and subsequent visits by paired t test. Data that were not normally distributed [SI, AIRg, disposition index (DI), and body mass index (BMI)] were log-transformed before analysis. As an index of early insulin secretion, we used acute insulin response to glucose (AIRg), calculated as the area under curve (AUC) over baseline from 2–10 min after the glucose bolus during the FSIGT. The DI (product of AIRg x SI) was used as an index of the compensatory adaptation to insulin resistance. The AUC of the C peptide response (AUCC peptide) to glucagon was used as an additional index of ß-cell function and was adjusted for glucose by taking the ratio of C peptide/glucose areas above baseline after glucagon. Insulin sensitivity (SI) was estimated by the MinMod analysis of insulin and glucose measured during the insulin-modified FSIGT (12).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Eight African-American subjects (six males; mean age, 46 ± 7 yr, BMI, 32.4 ± 6.3 kg/m2; negative GAD antibody) completed the study. The baseline characteristics of subjects are summarized in Table 1Go. All subjects started the study within 1 wk of hospitalization for hyperglycemic crisis, except subject 2, who had been hospitalized for hyperglycemic crisis 6 months before the study. Subject 3 had recently lost weight and had a lower BMI at presentation compared with other subjects, but his presentation with hyperglycemic crisis was otherwise consistent with atypical diabetes. With the exception of subject 4, whose lipase was mildly elevated at presentation, all subjects presented with normal lipase and amylase levels. At the time of the initial study, the acute hyperglycemic crisis had resolved in all subjects.


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  		TABLE 1. Baseline characteristics of study subjects

 
After intensive insulin therapy, fructosamine declined significantly by 3 wk (418 ± 110 to 227 ± 46 µmol/liter; P = 0.001), and HbA1c declined by 3 months (HbA1c, 13.5 ± 4.5% to 7.0 ± 1.5%; P = 0.003; Fig. 1Go). Despite achieving excellent glycemic control, insulin requirements decreased significantly by 3 months (0.72 ± 0.22 to 0.51 ± 0.18 U/kg; P = 0.02 vs. baseline).



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  		FIG. 1. Glycemic control with intensive insulin therapy. A, Fructosamine decreased significantly after 3 wk of intensive glucose control. B, HbA1c improved significantly after 3 months of treatment.

 
To determine the mechanism of improved control with reduced insulin requirements, we examined insulin secretion and insulin sensitivity from baseline to 3 months post treatment. AIRg, a measure of first phase ß-cell response to glucose, improved from 390 pmol/liter (range, 180–732 pmol/liter) at baseline to 1140 pmol/liter (range, 228-2508 pmol/liter; P = 0.05 vs. baseline) at 3 wk. This striking improvement was maintained at 3 months (P = 0.03 vs. baseline; Fig. 2AGo). Similarly, the DI (SI x AIRg), which reflects the ability of the ß-cell to compensate for reduced insulin sensitivity (13, 14), improved by 109% from baseline to 3 wk (baseline mean, 7.4 x 10–3 min–1; range, 0.4 to 24.0 x 10–3 min–1; 3 wk mean, 15.5 x 10–3 min1–; range, 3.1 to 55.5 x 10–3 min–1; P = 0.07), although this improvement did not reach nominal statistical significance. The improvement in disposition index was likewise sustained at 3 months (mean, 19.6 x 10–3 min–1; range, 3.6 to 56.2 x 10–3 min–1; P = 0.06 vs. baseline; Fig. 2BGo). The ß-cell response to the nonglucose secretagogue, glucagon (AUCC peptide/AUCglucose), likewise improved by 43.6% from baseline (5.49 ± 4.09) to 3 wk (9.90 ± 5.54; P = 0.02 vs. baseline) and remained elevated at 3 months (9.68 ± 4.61; P = 0.02 vs. baseline; see Fig. 2CGo). The improvement in AIRg at 3 months was highly correlated with the baseline glucagon response (Fig. 3Go; r = 0.78; P = 0.04).



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  		FIG. 2. Improvement in ß-cell function at baseline, 3 wk, and 3 months. A, AIRg improved at 3 wk from 390 to 1140 pmol/liter (P = 0.05 vs. baseline) and was maintained at 3 months (P = 0.03 vs. baseline). B, The DI improved from 7.4 x 10–3 min–1 at baseline to 15.5 x 10–3 min–1 at 3 wk (P = 0.07 vs. baseline) and 19.6 x 10–3 min–1 at 3 months (P = 0.06 vs. baseline). C, Improvement in C peptide response to glucagon at baseline, 3 wk, and 3 months. The AUCC peptide during the GST when adjusted for glucose (AUCC-peptide/AUCglucose) improved significantly after 3 wk (0.31 ± 0.23 to 0.55 ± 0.31; P = 0.02 vs. baseline) and remained significant after 3 months (0.31 ± 0.23 to 0.54 ± 0.26; P = 0.02 vs. baseline).

 


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  		FIG. 3. Correlation of change in AIRg and baseline C peptide response to glucagons (AUC). The changes in AIRg correlated significantly (r = 0.78; P = 0.05) with the basal AUC of C peptide in the GST.

 
In contrast to the marked improvement in ß-cell function by multiple measures, SI remained low throughout the study; thus, there was no improvement in SI despite the marked improvement in diabetes control. The mean baseline SI was 1.01 x 10–5 min–1/[pmol/l] (range, 0.10–2.90) and changed little at 3 months [mean, 1.09 x 10–5 min–1/(pmol/liter); range, 0.59 to 2.47; P = 0.87; Fig. 4Go].



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  		FIG. 4. SI was unchanged from baseline to 3 wk and 3 months.

 
Because subject 2 was recruited more than 1 wk after the hyperglycemic crisis, we reanalyzed the data after excluding this subject. Although AIRg, SI, and glucagon-stimulated C peptide response were not substantially changed with exclusion of this subject, the improvement in the DI was significant at 3 wk (baseline mean, 6.8 x 10–3 min–1; range, 0.4 to 24.0 x 10–3 min–1; 3 wk mean, 17.1 x 10–3 min–1; range, 3.1 to 55.5 x 10–3 min–1; P = 0.03) and was sustained at 3 months (mean, 21.9 x 10–3 min–1; range, 9.9 to 56.2 x 10–3 min–1; P = 0.03 vs. baseline).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Typical T2DM is characterized by an inexorable progressive deterioration in ß-cell function in the milieu of insulin resistance (15). Improved control is generally difficult despite increasing therapy in the absence of significant lifestyle changes (15). The subjects in the current study presented with hyperglycemic crisis of presumably short duration. Control was achieved rapidly using an intensive insulin regimen to eliminate glucotoxicity. The subjects experienced a rapid and significant restoration of ß-cell function, associated with markedly improved diabetes control with near-normal glucose and HbA1c levels. Paradoxically, insulin requirements declined despite the improved control. The mechanism of this recovery was entirely from the restoration of pancreatic ß-cell function. ß-Cell function was poor 1 wk after treatment of the hyperglycemic crisis, but showed marked improvement by 3 wk and no additional change at 3 months. In contrast, insulin sensitivity did not improve either in the short term or in the long term, and thus improved SI cannot be the mechanism for the improved diabetes control. By induction, remission in atypical diabetes seems likely to result from the restoration of ß-cell function rather than a change in SI. To our knowledge, this is the first study to characterize the immediate, short-term, and intermediate-term measures of insulin secretion, SI, and diabetes control in African-American subjects presenting with atypical diabetes. Our study supports other recent work suggesting that ß-cell recovery drives improved glycemic control in atypical diabetes (16).

Several mechanisms might explain the rapid response of these subjects despite presentation with very high glucose levels and/or ketosis. Chronic hyperglycemia and glucotoxicity might reduce insulin action and worsen ß-cell function and would clearly have improved after intensive insulin therapy (17). However, sustained improvement is difficult to achieve in typical T2DM (18), thus suggesting that a reversible ß-cell defect in the setting of insulin resistance characterized the atypical diabetes patients in this study. Interestingly, the baseline C peptide response to glucagon was predictive of the subsequent course, suggesting that the diabetes-precipitating events might have resulted from impaired glucose-stimulated insulin secretion rather than a decline in ß-cell mass, and the potential for improvement might be related to baseline ß-cell mass. This subgroup of diabetic subjects may be more susceptible to glucotoxicity because of genetic or environmental factors, such as diet. Anecdotally, most subjects presenting with atypical diabetes provided a history of quenching their polydipsia with high sucrose-containing beverages, which may have driven short-term glucotoxicity and permitted rapid turnaround of the disease with adequate therapy. However, if glucotoxicity was the explanation for the rapid deterioration and recovery in ß-cell function, the failure to see any improvement in SI with improved glycemic control would be unexpected. Subjects presenting with hyperglycemic crisis may be particularly vulnerable to glucotoxic effects leading to ß-cell dysfunction.

Subjects who showed the least improvement in AIRg differed from the others in having been enrolled 6 months after admission (subject 2) or not reaching optimal glucose control during the study (subject 6). Although these findings might argue that our early intervention in the remaining subjects was key to the rapid ß-cell recovery, other explanations are possible. Subjects with atypical diabetes may not be a homogeneous group, and the syndrome is difficult to define exactly. For example, ketosis was present in only three of our subjects at presentation. Furthermore, after the completion of this study, we identified a proline insertion in the transactivation domain of the pancreas-duodenum homeobox gene (PDX1) (19) in subject 2, which we have recently found to be common among African-American individuals (Elbein, S. C., unpublished observations). This mutation was present only in subject 2, not in the other subjects. Other mutations were recently reported in the PAX4 gene in ketosis-prone diabetes (Mauvais-Jarvis, F. personal communication and Late Breaking Abstract, American Diabetes Association Scientific Sessions, 2004). Defects in such key regulators of pancreatic ß-cell mass and function might explain heterogeneity in presentation and in recovery. PAX4 mutation has not been assessed in this study population to date.

In summary, ß-cell function is rapidly reversible after only 3 wk of intensive insulin treatment in subjects with atypical diabetes. The degree of improvement is highly correlated with ß-cell reserve at the time of discharge after the acute episode. Clinically, this study suggests that intensive insulin therapy, which was well tolerated and safe, might be the initial treatment of choice in such patients, although our intent in these studies was not to test the therapeutic intervention but, rather, to achieve rapid glycemic control and to follow the pathophysiology of the recovery. We show clearly that improved ß-cell function drives this recovery, but that insulin resistance remains present despite the markedly improved control. The long-term prognosis for these subjects is uncertain, but those we continue to follow have experienced additional reductions in their insulin doses and stable glycemic control.


   Acknowledgments
 
We appreciate the support of the nursing and laboratory staff of GCRC at the University of Arkansas Medical School and the valuable consultation of the GCRC statistician, Horace J. Spencer. We also thank the patients who participated in this study.


   Footnotes
 
This work was supported by an Endocrine Fellows Foundation grant and General Clinical Research Center Grant M01-RR-14288 from the National Center for Research Resources, NIH (to University of Arkansas for Medical Sciences).

Abbreviations: AIRg, Acute insulin response to glucose; AUC, area under the curve; BMI, body mass index; DI, disposition index; DKA, diabetic ketoacidosis; FSIGT, frequently sampled iv glucose tolerance test; GAD, glutamic acid decarboxylase; GST, glucagon stimulation test; HbA1c, hemoglobin A1c; SI, insulin sensitivity; T2DM, type 2 diabetes mellitus.

Received June 2, 2004.

Accepted September 2, 2004.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Banerji MA, Chaiken RL, Huey H, Tuomi T, Norin AJ, Mackay IR, Rowley MJ, Zimmet PZ, Lebovitz HE 1994 GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. Diabetes 43:741–745[Abstract]
  2. Umpierrez GE, Woo W, Hagopian WA, Isaacs SD, Palmer JP, Gaur LK, Nepom GT, Clark WS, Mixon PS, Kitabchi AE 1999 Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis. Diabetes Care 22:1517–1523[Abstract/Free Full Text]
  3. Tan KC, Mackay IR, Zimmet PZ, Hawkins BR, Lam KS 2000 Metabolic and immunologic features of Chinese patients with atypical diabetes mellitus. Diabetes Care 23:335–338[Abstract]
  4. Tanaka K, Moriya T, Kanamori A, Yajima Y 1999 Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients. Diabetes Res Clin Pract 44:137–146[CrossRef][Medline]
  5. Pinero-Pilona A, Raskin P 2001 Idiopathic type 1 diabetes. J Diabetes Complications 15:328–335[CrossRef][Medline]
  6. Maldonado M, Hampe CS, Gaur LK, D’Amico S, Iyer D, Hammerle LP, Bolgiano D, Rodriguez L, Rajan A, Lernmark A, Balasubramanyam A 2003 Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and ß-cell functional classification, prospective analysis, and clinical outcomes. J Clin Endocrinol Metab 88:5090–5098[Abstract/Free Full Text]
  7. Kitabchi AE 2003 Ketosis-prone diabetes: a new subgroup of patients with atypical type 1 and type 2 diabetes? J Clin Endocrinol Metab 88:5087–5089[Free Full Text]
  8. Umpierrez GE, Clark WS, Steen MT 1997 Sulfonylurea treatment prevents recurrence of hyperglycemia in obese African-American patients with a history of hyperglycemic crises. Diabetes Care 20:479–483[Abstract]
  9. McFarlane SI, Chaiken RL, Hirsch S, Harrington P, Lebovitz HE, Banerji MA 2001 Near-normoglycaemic remission in African-Americans with type 2 diabetes mellitus is associated with recovery of ß cell function. Diabet Med 18:10–16[Medline]
  10. Banerji MA, Chaiken RL, Lebovitz HE 1995 Prolongation of near-normoglycemic remission in black NIDDM subjects with chronic low-dose sulfonylurea treatment. Diabetes 44:466–470[Abstract]
  11. Umpierrez GE, Casals MM, Gebhart SP, Mixon PS, Clark WS, Phillips LS 1995 Diabetic ketoacidosis in obese African-Americans. Diabetes 44:790–795[Abstract]
  12. Bergman RN, Ider YZ, Bowden CR, Cobelli C 1979 Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677
  13. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP 1993 Quantification of the relationship between insulin sensitivity and ß-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42:1663–1672[Abstract]
  14. Bergman RN 1989 Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38:1512–1527[Abstract]
  15. Turner RC 1998 The U.K. Prospective Diabetes Study. A review. Diabetes Care 21(Suppl 3):C35–C38
  16. Mauvais-Jarvis F, Sobngwi E, Porcher R, Riveline JP, Kevorkian JP, Vaisse C, Charpentier G, Guillausseau PJ, Vexiau P, Gautier JF 2004 Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of ß-cell dysfunction and insulin resistance. Diabetes 53:645–653[Abstract/Free Full Text]
  17. Garvey WT, Olefsky JM, Griffin J, Hamman RF, Kolterman OG 1985 The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 34:222–234[Abstract]
  18. Henry RR 1996 Glucose control and insulin resistance in non-insulin-dependent diabetes mellitus. Ann Intern Med 124:97–103[Abstract/Free Full Text]
  19. Hani EH, Stoffers DA, Chevre JC, Durand E, Stanojevic V, Dina C, Habener JF, Froguel P 1999 Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus. J Clin Invest 104:R41–R48



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