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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 1 76-80
Copyright © 2000 by The Endocrine Society

Original Studies

Insulin and Glucagon Secretion in Patients with Slowly Progressing Autoimmune Diabetes (LADA)1

ÅsaLinda Carlsson, Göran Sundkvist, Leif Groop and Tiinamaija Tuomi

Department of Endocrinology, University of Lund, S-205 02 Malmo, Sweden (Å.L.C., G.S., L.G., T.T.) and the Department of Internal Medicine, Helsinki University Central Hospital (T.T.), Helsinki, Finland

Address all correspondence and requests for reprints to: Tiinamaija Tuomi, M.D., Wallenberg Laboratory, Department of Endocrinology, University of Lund, S-205 02 Malmo, Sweden.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
To metabolically characterize patients with slowly progressing autoimmune diabetes (LADA) of short duration we measured insulin, C peptide, and glucagon responses to glucose and arginine at three blood glucose levels (fasting and 14 and 28 mmol/L) in 11 patients with LADA, 11 patients with type 2 diabetes, and 14 healthy control subjects matched for age and body mass index. The acute insulin response to arginine was impaired in LADA vs. type 2 diabetes at all glucose levels, with the greatest impairment in the maximally stimulated insulin concentrations (P < 0.04). In contrast, ß-cell sensitivity to glucose was unaltered in LADA and type 2 diabetes. The glucagon concentrations were elevated in both LADA and type 2 diabetic patients compared with healthy control subjects (P < 0.02), but did not differ between the diabetic groups. In conclusion, patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in maximally stimulated ß-cell capacity than patients with type 2 diabetes.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ABOUT 10% of patients diagnosed with type 2 diabetes have circulating autoantibodies to either islet cell cytoplasmic antigens (1, 2, 3) or, more frequently, glutamic acid decarboxylase (GADab) (4, 5, 6, 7, 8, 9). This subgroup, also referred to as latent autoimmune diabetes in adults (LADA) (5, 9), has been included in the new WHO proposal for classification of diabetes as a slowly progressing form of type 1 diabetes (10). Obviously LADA shares features with both type 1 and type 2 diabetes. Although insulin secretion is better preserved in the slowly progressing than in the rapidly progressing form of autoimmune diabetes (9, 11), insulin secretion tends to deteriorate with time in LADA patients (7, 8, 9, 12). Assessments of insulin secretion in the earlier studies was based upon crude measurements of ß-cell function, such as fasting or glucagon-stimulated C peptide concentrations (3, 5, 7, 13, 14) or the HOMA model of ß-cell function (8). These tests would hardly stress the ß-cells to their limits to allow detection of more subtle defects in ß-cell capacity. Also, in most studies the patients have had a relatively long duration of the disease, which makes it difficult to discern between primary (autoimmune) and secondary (chronic hyperglycemia) defects in insulin secretion. Glucagon levels and responses differ between type 1 and type 2 diabetes during the course of the disease (15, 16, 17, 18, 19). No information is available on glucagon secretion in patients with LADA. The aim of this study was to compare insulin and glucagon secretion and insulin sensitivity between LADA and type 2 diabetic patients of short duration and healthy control subjects.


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

Between 1994–1996, 573 consecutive patients diagnosed with type 2 diabetes in Malmö, Sweden were tested for GADab. Of them, 49 (8.5%) were GADab positive (GADab+). Eleven of these GADab+ patients met the criteria (>30–70 yr of age, no insulin treatment during the first 12 months) and accepted to participate in an iv glucose-arginine test. They were matched for age, sex, and body mass index (BMI) with 11 GADab-negative (GADab-) type 2 diabetic patients diagnosed during the same period. Fourteen nondiabetic individuals without first degree family history of diabetes served as control subjects (Table 1Go). Informed consent was obtained from all participants. The local ethics committee at Lund University approved the study.


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  		Table 1. Clinical characteristics of the subjects

 
Glucose-arginine test

Insulin secretion was measured during iv stimulation with glucose and arginine after an overnight fast according to the method described by Ward et al. (20) (Fig. 1Go). Blood samples were drawn for measurement of glucose, insulin, and C peptide (the latter only for diabetic patients) 5 and 2 min before as well as 2, 3, 4, and 5 min after an iv injection of 5 g arginine hydrochloride. Glucagon was measured only at -5 and -2 min. This procedure was carried out in the basal state and after the blood glucose concentration had been raised to 14 and 28 mmol/L [mean coefficient of variation (CV), 8.1% and 7.0%, respectively) by a variable iv infusion of 20% glucose. Blood glucose was measured every 5 min to maintain the desired blood glucose concentration. A 2.5-h resting period was allowed before the blood glucose was raised to 28 mmol/L to avoid the priming effect of hyperglycemia. After new baseline samples, the glucose infusion was restarted, and blood glucose was raised to 28 mmol/L over 25–30 min. The insulin response to glucose at fasting blood glucose and at blood glucose levels of 14 and 28 mmol/L was calculated as the mean of the insulin levels at -2 and -5 min. The acute insulin response to arginine (AIRarg) was calculated as the mean of the 2–5 min values after subtraction of the mean of the prestimulus values. The C peptide response to glucose, acute C peptide response (ACRarg) to arginine, and glucagon response to glucose (GRgluc) were calculated in the same manner.



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  		Figure 1. Serum insulin concentrations (y-axis) during the glucose-arginine test in patients with LADA (•; n = 11) or type 2 diabetes ({circ}; n = 11) and in nondiabetic control subjects ({blacktriangleup}; n = 14). The insulin concentrations are given at three blood glucose levels (fasting, 14 mmol/L, and 28 mmol/L) 5 and 2 min before as well as 2, 3, 4, and 5 min after an injection of arginine (marked with arrows).

 
The AIRarg at a blood glucose level exceeding 25 mmol/L is considered to represent the maximal insulin secretory capacity (20). The glucose potentiation of ß-cells was estimated as the slope between AIRarg at fasting and at a blood glucose level of 14 mmol/L (slopeAIR = {Delta}AIRarg/{Delta}glucose) (21). From this equation, the ß-cell sensitivity to glucose was calculated as the blood glucose level at which half-maximal AIR to arginine occurred (20).

Laboratory methods

Serum insulin concentrations were measured using a double antibody enzyme-linked immunosorbent assay (DAKO Corp., Cambridgeshire, UK) with an interassay CV of 8.9%. Serum C peptide concentrations were measured by RIA (Linco Research, Inc., St. Charles, MO) with an interassay CV of 9.8%. Plasma glucagon concentrations were measured by RIA (Linco Research, Inc.). In the assay, pancreatic glucagon had a cross-reactivity with enteric glucagon of less than 0.1% and an intraassay CV of 3.6%. Blood glucose was measured in duplicate using the glucose oxidase method. GAD antibodies were measured from frozen serum samples by a radioimmunoprecipitation assay employing recombinant human [35S]GAD65 produced by in vitro transcription/translation as described previously (9). At the Combined Autoantibody Workshop, the specificity of the assay was 99%, and the sensitivity was 75% (22).

Statistical analysis

Statistical analyses were performed using the BMDP new system, version 1.12, for Windows (BMDP Statistical Software, Inc., Los Angeles, CA). Data are given as the mean ± SD or as the median (75–25% interquartile range) unless indicated otherwise. The statistical significance of the difference between groups was tested using the Mann-Whitney individual rank sum test.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Patients with LADA and type 2 diabetes were matched with respect to sex, BMI, and age at diagnosis of diabetes (Table 1Go). The LADA patients had a slightly shorter duration of diabetes than the type 2 diabetic patients (1.7 ± 1.2 vs. 3.2 ± 1.2 yr; P = 0.01). Insulin resistance according to the HOMA model (23) did not significantly differ between LADA and type 2 diabetic patients [median (75–25% interquartile range), 2.1 (3.9) vs. 3.2 (3.5)]. However, both diabetic groups differed significantly from the control subjects [median (75–25% interquartile range), 0.4 (1.3); P < 0.03; Table 1Go].

Insulin and C peptide responses

Both diabetic groups showed significantly lower insulin responses to glucose and glucose plus arginine compared with the control subjects of similar age and BMI (Fig. 1Go). Insulin secretion stimulated by glucose was decreased in LADA compared with type 2 diabetic patients at 28 mmol/L (12.2 ± 9.0 vs. 24.3 ± 25.8 mU/L; P = 0.04; Fig. 2AGo). The acute insulin response to glucose and arginine was significantly lower in LADA compared with type 2 diabetic patients at all blood glucose concentrations [AIRargf, 23.7 ± 19.6 vs. 37.2 ± 22.0 mU/L (P = 0.03); AIRarg14, 28.6 ± 17.2 vs. 50.8 ± 29.0 mU/L (P = 0.04); AIRarg28, 42.1 ± 36.1 vs. 80.9 ± 62.6 mU/L (P = 0.04); Fig. 2BGo]. Similarly, the C peptide responses to glucose and arginine were lower in LADA than in type 2 diabetic patients (Fig. 2Go, A and B).



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  		Figure 2. Serum insulin and C peptide response to iv glucose (A) and acute insulin or C peptide responses (AIRarg, ACRarg) to glucose and arginine (B) at three blood glucose levels (fasting, 14 mmol/L, and 28 mmol/L) in patients with LADA (•; n = 11) or type 2 diabetes ({circ}; n = 11) and in nondiabetic control subjects ({blacktriangleup}; n = 14). AIR and ACR were calculated as the mean of the 2–5 min values after subtraction of the mean of the prestimulus values. Data are shown as the mean ± SEM. Note that the y-axis in B has a logarithmic scale. *, P = 0.05; **, P = 0.04; ***, P = 0.03 (LADA vs. type 2 diabetes).

 
There was no significant difference in the glucose potentiation of ß-cell function between LADA and type 2 diabetes, whereas both diabetic groups differed significantly from the control subjects [median (75–25% interquartile range): slopeAIR, 1.3 (1.6) and 2.1 (3.3) vs. 5.4 (7.3); P < 0.0002]. ß-Cell sensitivity to glucose was unaffected in the two diabetic groups [median (75–25% interquartile range): LADA vs. type 2 diabetes, 8.6 (12.1) vs. 10.7 (13.5) mmol/L] and was indistinguishable from that in control subjects [8.1 (3.9) mmol/L].

Glucagon response

The glucagon concentration was decreased by increasing the glucose concentration in the control subjects (Fig. 3Go). In the diabetic groups the glucagon concentration was elevated and less suppressed by glucose compared with that in the control subjects [LADA and type 2 diabetic patients vs. control subjects: GRglucf, 64.4 ± 18.2 and 68.7 ± 30.8 vs. 44.8 ± 12.6 ng/L (P <= 0.02); GRgluc14, 56.4 ± 19.1 and 60.1 ± 24.1 vs. 31.9 ± 9.2 ng/L (P <= 0.001); GRgluc28, 39.2 ± 12.0 and 42.9 ± 19.5 vs. 24.6 ± 7.6 ng/L (P <= 0.007)]. No significant difference was seen between LADA and type 2 diabetic patients with respect to the glucagon concentration (Fig. 3Go).



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  		Figure 3. Glucagon response to iv glucose at three blood glucose levels (fasting, 14 mmol/L, and 28 mmol/L) in patients with LADA (•; n = 11) or type 2 diabetes ({circ}; n = 11) and in nondiabetic control subjects ({blacktriangleup}; n = 14). Data are shown as the mean ± SEM. *, P < 0.02; **, P < 0.007; ***, P < 0.001 (LADA and type 2 diabetes vs. control subjects).

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study provided novel information on the pancreatic defects in patients with LADA, which can be used to distinguish them from patients with classical type 2 diabetes as well as from patients with classical type 1 diabetes. The tools used allowed careful quantification of ß-cell capacity and sensitivity (for both insulin and glucagon secretion). Although patients with LADA shared insulin resistance and elevated glucagon levels with patients with type 2 diabetes, they exhibited a much more severe defect in insulin secretion. Prospective studies have previously shown that GADab+ patients deteriorate in their insulin secretion over time and that they are more likely to require insulin therapy than GADab- patients (7, 8, 12). Although they in this respect resemble patients with type 1 diabetes, we have shown that the LADA patients have higher C peptide levels even after 10 yr of diabetes than patients with adult-onset type 1 diabetes (9). Also, in the present study the LADA patients did not require insulin treatment and had a mean fasting C peptide concentration of 0.64 ± 0.32 nmol/L after a disease duration of 1.7 ± 1.2 yr, separating them from patients that could be classified as having type 1 diabetes. However, it has not been known whether a difference in insulin secretory capacity between LADA and type 2 diabetes can be detected at the time of diagnosis or soon thereafter. We showed in patients with short term diabetes that despite similar fasting C peptide concentrations, a marked difference in ß-cell function between LADA and type 2 diabetes could be observed at a high glucose concentration (28 mmol/L) with and without stimulation with arginine.

Some important conclusions can be drawn from these findings. The ß-cell defect characteristic of LADA is not restricted to stimulation with glucose, suggesting that it is not due to defects in glucose metabolism in the ß-cell. The impaired insulin secretion after stimulation with arginine at glucose concentrations of 14 and 28 mmol/L, rather, suggests a reduction of the maximal ß-cell capacity (20) consistent with an irreversible autoimmune destruction of the ß-cells. The defect in insulin secretion is hardly a consequence of chronic hyperglycemia, as the two patient groups had similar glycemic control. Neither could it be a consequence of better insulin sensitivity, as insulin secretion adjusted for insulin sensitivity (HOMA) was impaired in both LADA and type 2 diabetic patients.

Despite an accelerated deterioration of ß-cell function, the LADA patients share many features with common type 2 diabetes, e.g. elevated glucagon levels and insulin resistance. The elevated glucagon concentrations may have several metabolic consequences. First, glucagon stimulates insulin secretion, and the elevated glucagon concentrations may serve to maintain insulin secretion and explain why LADA patients rarely develop total ß-cell dysfunction (15, 16, 17, 18, 19). Glucagon is also a potent stimulator of gluconeogenesis and glycogen breakdown, resulting in increased hepatic glucose output. Although we did not measure hepatic glucose production in this study, we have previously shown that patients with LADA have an enhanced basal rate of hepatic glucose production, which cannot be suppressed by insulin (11). This study provides a potential explanation for the hepatic insulin resistance, i.e. elevated glucagon levels.

In conclusion, metabolically LADA shares features with both type 1 and type 2 diabetes. With the former, LADA patients share a severe and progressing defect in ß-cell function. With the latter, they share insulin resistance and elevated glucagon levels. These data further emphasize the need to consider LADA as a diabetic subgroup distinct from both type 1 and type 2 diabetes.


   Acknowledgments
 
Gertrud Ahlqvist, Britt Bruveris-Svenburg, Marianne Lundberg, and Christina Rosborn are acknowledged for skillful technical assistance, and Dr. Hillevi Larsson for help with recruiting the nondiabetic control subjects.


   Footnotes
 
1 This work was supported by grants from the Påhlsson Foundation, the Medical Faculty of the Lund University, the Malmö University Hospital, the Swedish Society of Medicine, the Crafoord Foundation, the Swedish Medical Doctors Association, and the Malmö Diabetes Association. Back

Received May 25, 1999.

Revised August 31, 1999.

Accepted September 9, 1999.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Irvine WJ, Gray RS, McCallum CJ, Duncan LJP. 1977 Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycemic agents. Lancet. 1025–1027.
  2. Groop L, Bottazzo GF, Doniach D. 1986 Islet cell antibodies identify latent type 1 diabetes in patients aged 35–75 years at diagnosis. Diabetes. 35:237–241.[Abstract]
  3. Landin-Olsson M, Nilsson KO, Lernmark Å, Sundkvist G. 1990 Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus. Diabetologia. 33:561–568.[CrossRef][Medline]
  4. Hagopian WA, Karlsen AE, Gottsäter A, et al. 1993 Quantitative assay using recombinant human islet glutamic acid decarboxylase .(GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type. J Clin Invest. 91:368–374.
  5. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. 1993 Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes. 42:359–362.[Abstract]
  6. Zimmet PZ, Tuomi T, Mackay IR, et al. 1994 Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabetic Med. 11:299–303.[Medline]
  7. Niskanen LK, Tuomi T, Karjalainen J, Groop LC, Uusitupa MI. 1995 GAD antibodies in NIDDM. Ten-year follow-up from the diagnosis. Diabetes Care. 18:1557–1565.[Abstract]
  8. Turner R, Stratton I, Horton V, et al. 1997 UKPDS 25: autoantibodies to islet cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet. 350:1288–1293.[CrossRef][Medline]
  9. Tuomi T, Carlsson ÅL, Li H, et al. 1999 Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes. 48:150–157.[Abstract]
  10. Alberti KGMM, Zimmet P, for the WHO Consultation. 1998 Definition, diagnosis and classification of diabetes mellitus and its complications. I. Diagnosis and classification of diabetes mellitus. Diabetic Med. 15:539–551.[CrossRef][Medline]
  11. Groop LC, Eriksson J, Ekstrand A, Franssila Kallunki A, Saloranta C, Miettinen A. 1991 Metabolic characteristics of autoimmune diabetes mellitus in adults. Diabetologia. 34:46–51.[CrossRef][Medline]
  12. Gottsäter A, Landin-Olsson M, Lernmark Å, Fernlund P, Sundkvist G, Hagopian W. 1995 Glutamate decarboxylase antibody levels predict rate of beta-cell decline in adult-onset diabetes. Diabetes Res Clin Pract. 27:133–140.[CrossRef][Medline]
  13. Groop L, Groop PH, Koskimies S. 1986 Relationship between B-cell function and HLA antigens in patients with type 2 non-insulin-dependent) diabetes. Diabetologia. 29:757–760.[CrossRef][Medline]
  14. Gottsäter A, Landin-Olsson M, Fernlund P, Lernmark Å, Sundkvist G. 1993 ß-Cell function in relation to islet cell antibodies during the first 3 yr after clinical diagnosis of diabetes in type II diabetic patients. Diabetes Care. 16:902–910.[Abstract]
  15. Aguilar Parada E, Eisentraut AM, Unger RH. 1969 Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci. 257:415–419.[Medline]
  16. Unger RH, Aguilar Parada E, Muller WA, Eisentraut AM. 1970 Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest. 49:837–848.
  17. Samols E, Tyler J, Marks V. 1972 Glucagon-insulin relationships. In: Lefebvre PJ, Unger RH. eds. Glucagon. Molecular physiology, clinical and theraphutic implications. Oxford: Pergamon Press; 151–173.
  18. Raskin P, Aydin I, Unger RH. 1976 Effect of insulin on the exaggerated glucagon response to arginine stimulation in diabetes mellitus. Diabetes. 25:227–229.[Abstract]
  19. Bolli G, de Feo P, Compagnucci P, et al. 1983 Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes. 32:134–141.[Abstract]
  20. Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte Jr D. 1984 Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest. 74:1318–1328.
  21. Halter JB, Graf RJ, Porte Jr D. 1979 Potentiation of insulin secretory responses by plasma glucose levels in man: evidence that hyperglycemia in diabetes compensates for impaired glucose potentiation. J Clin Endocrinol Metab. 48:946–954.[Medline]
  22. Verge CF, Stenger D, Bonifacio E, et al. 1998 Combined use of autoantibodies IA-2ab, GADab, IAA, ICA) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes. 47:1857–1866.[Abstract]
  23. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28:412–419.[CrossRef][Medline]



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