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. 2018 Dec 22;13(1):230.
doi: 10.1186/s13023-018-0970-8.

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism

Alena Welters  1 , Thomas Meissner  2 , Jürgen Grulich-Henn  3 , Elke Fröhlich-Reiterer  4 , Katharina Warncke  5 , Klaus Mohnike  6 , Oliver Blankenstein  7 , Ulrike Menzel  8 , Nicolin Datz  9 , Esther Bollow  10 , Reinhard W Holl  10   11
Affiliations

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism

Alena Welters et al. Orphanet J Rare Dis. .

Abstract

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Little is known about the management and long-term glycaemic control of CHI patients with diabetes after pancreatic surgery. We searched the German/Austrian DPV database and compared the course of 42 CHI patients with diabetes to that of patients with type 1 diabetes mellitus (T1DM). Study groups were compared at diabetes onset and after a follow-up period of 6.1 [3.3-9.7] (median [interquartile range]) years.

Results: The majority of CHI patients with diabetes were treated with insulin (85.2% [70.9-99.5] at diabetes onset, and 90.5% [81.2-99.7] at follow-up). However, compared to patients with T1DM, significantly more patients in the CHI group with diabetes were treated with conventional insulin therapy (47.8% vs. 24.4%, p = 0.03 at diabetes onset, and 21.1% vs. 6.4% at follow-up, p = 0.003), and only a small number of CHI patients were treated with insulin pumps. Daily insulin dose was significantly lower in CHI patients with diabetes than in patients with T1DM, both at diabetes onset (0.3 [0.2-0.5] vs. 0.6 IE/kg/d [0.4-0.8], p = 0.003) and follow-up (0.8 [0.4-1.0] vs. 0.9 [0.7-1.0] IE/kg/d, p = 0.02), while daily carbohydrate intake was comparable in both groups. Within the first treatment year, HbA1c levels were significantly lower in CHI patients with diabetes (6.2% [5.5-7.9] vs. 7.2% [6.5-8.2], p = 0.003), but increased to a level comparable to that of T1DM patients at follow-up. Interestingly, in CHI patients, the risk of severe hypoglycaemia tends to be higher only at diabetes onset (14.8% vs. 5.8%, p = 0.1).

Conclusions: In surgically treated CHI patients insulin treatment needs to be intensified in order to achieve good glycaemic control. Our data furthermore emphasize the need for improved medical treatment options for patients with diazoxide- and/or octreotide-unresponsive CHI.

Keywords: Congenital hyperinsulinism; DPV initiative; Diabetes; Pancreatectomy.

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Conflict of interest statement

Ethics approval and consent to participate

The DPV initiative and the analysis of anonymized data related to quality of care were approved by the ethics committee of the University of Ulm. The institutional review boards at each participating centre confirmed protection of patient primary rights.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Selected characteristics of CHI patients with diabetes compared to patients with T1DM. a Median duration of diabetes (years); n = 27 (diabetes onset) and 42 (follow-up) CHI patients with diabetes, and n = 54,747 (diabetes onset) and 65,982 (follow-up) patients with T1DM; b Median period between pancreatic surgery and diabetes onset in CHI patients with diabetes; n = 22; c BMI (kg/m2); n = 19 (diabetes onset) and 37 (follow-up) CHI patients with diabetes, and n = 33,326 (diabetes onset) and 58,388 (follow-up) patients with T1DM d Age at diabetes onset; n = 27 CHI patients with diabetes, and n = 54,774 patients with T1DM. Significance determined by p < 0.05 using Wilcoxon test
Fig. 2
Fig. 2
Management of diabetes in CHI patients with diabetes compared to patients with T1DM. a Proportion of CHI patients with diabetes treated with insulin or oral antidiabetic drugs; n = 27 (diabetes onset) and 42 (follow-up) CHI patients with diabetes. b Insulin regimen in CHI patients with diabetes compared to patients with T1DM; n = 23 (diabetes onset) and 38 (follow-up) CHI patients with diabetes, and n = 51,704 (diabetes onset) and 62,829 (follow-up) patients with T1DM. c Number of injection times per day in CHI patients with diabetes compared to patients with T1DM; n = 20 (diabetes onset) and 29 (follow-up) CHI patients with diabetes, and n = 43,378 (diabetes onset) and 39,546 (follow-up) patients with T1DM. d Proportion of insulin analogues as basal insulin supplementation; n = 20 (diabetes onset) and 29 (follow-up) CHI patients with diabetes, and n = 43,378 (diabetes onset) and 39,546 (follow-up) patients with T1DM. All values are means. *P < 0.05. Significance determined by p < 0.05 using χ2-test
Fig. 3
Fig. 3
Frequency of severe hypoglycaemia in CHI patients with diabetes compared to patients with T1DM. Severe hypoglycaemia; n = 27 (diabetes onset) and 42 (follow-up) CHI patients with diabetes, and n = 54,706 (diabetes onset) and 65,927 (follow-up) patients with T1DM. All values are means. Significance determined by p < 0.05 using χ2-test (and McNemar test)
Fig. 4
Fig. 4
Glycaemic control in CHI patients with diabetes compared to patients with T1DM. HbA1c level; n = 25 (diabetes onset) and 42 (follow-up) CHI patients with diabetes, and n = 52,825 (diabetes onset) and 63,368 (follow-up) patients with T1DM. All values are median ± lower and upper quartile. *P < 0.05. Significance determined by p < 0.05 using Wilcoxon test (and t-test)
Fig. 5
Fig. 5
Residual beta cell function at diabetes onset (a) and at follow-up (b) in CHI patients with diabetes compared to patients with T1DM. C-peptide secretion; n = 11 (diabetes onset) and 8 (follow-up) CHI patients with diabetes, and n = 13,746 (diabetes onset) and 3497 (follow-up) patients with T1DM. All values are means. Significance determined by p < 0.05 using χ2-test
Fig. 6
Fig. 6
Insulin requirement and carbohydrate intake in CHI patients with diabetes compared to patients with T1DM. a Total daily insulin dose (IE/d); n = 23 (diabetes onset) and 38 (follow-up) CHI patients with diabetes, and n = 51,704 (diabetes onset) and 62,829 (follow-up) patients with T1DM. b Daily insulin dose per kg body weight (IE/kg/d); n = 18 (diabetes onset) and 35 (follow-up) CHI patients with diabetes, and n = 32,304 (diabetes onset) and 57,206 (follow-up) patients with T1DM. c Total daily basal insulin dose (IE/d); n = 22 (diabetes onset) and 35 (follow-up) CHI patients with diabetes, and n = 51,145 (diabetes onset) and 62,440 (follow-up) patients with T1DM. d Total daily prandial insulin dose (IE/d); n = 21 (diabetes onset) and 37 (follow-up) CHI patients with diabetes, and n = 50,454 (diabetes onset) and 62,246 (follow-up) patients with T1DM. e Total daily carbohydrate intake (CU/d); n = 18 (diabetes onset) and 34 (follow-up) CHI patients with diabetes, and n = 45,494 (diabetes onset) and 58,655 (follow-up) patients with T1DM. f Daily carbohydrate intake per kg body weight (CU/kg/d); n = 16 (diabetes onset) and 31 (follow-up) CHI patients with diabetes, and n = 28,202 (diabetes onset) and n = 53,380 (follow-up) patients with T1DM. All values are median ± lower and upper quartile. *P < 0.05. Significance determined by p < 0.05 using Wilcoxon test
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