Diabetes mellitus as a consequence of acute severe pancreatitis: Unraveling the mystery

Table 1 Summaries all the studies examining endocrine insufficiency after episode of acute pancreatitis

Ref.	Study design	Number of patients evaluated for endocrine function	Severity of AP	Etiology of pancreatitis	Follow up period	Test to diagnose endocrine function	Pre-diabetic (%)	Diabetes (%)	Insulin treatment (%)	Comment
Ohlsén et al[28], 1968, Sweden	Prospective case control	23	-	-	Not stated	IV GTT, glucose infusion test	4 (17)	0 (0)	0 (0)	-
Johansen and Ornshlot[29], 1972, Denmark	Prospective cohort	22	-	Alcohol 4 (18%). Biliary 11 (50%). Others 3 (14%). Idiopathic 4 (18%)	24	OGTT	0 (0)	4 (18)	-	-
Olszewski et al[30], 1978, Poland	Prospective case control	25	-	-	12	OGTT, BI	-	7 (28)	-	-
Seligson et al[31], 1982, Sweden	Prospective cohort	9	All severe	-	63	OGTT	3 (33)	2 (22)	-	-
Angelini et al[32], 1984, Italy	Prospective cohort	19	All severe	-	25	OGTT	7 (36)	2 (10.5)	-	-
Eriksson et al[33], 1992, Finland	Prospective cohort	36	Mild: 16 (44%). Severe: 20 (56%)	Alcohol: 28 (78%). Biliary: 2 (6%). Post-ERCP: 2 (6%). Idiopathic: 4 (10%)	74	OGTT	4 (11)	19 (53)	9 (25)	Diabetes was more in surgical necrosectomy compared to conservative approach (100% vs 26%, P = 0.0004)
Doepel et al[34], 1993, Finland	Prospective cohort	37	All severe	Alcohol: 28 (76%). Biliary: 3 (8%). Post-ERCP: 2 (5%). Idiopathic: 4 (11%)	74	BG, C-peptide, HbA1, OGGT	-	20 (54)	9 (45)	Diabetes was more in surgical necrosectomy compared to no necrosectomy (100% vs 29.1%, P < 0.005). Diabetes was more common with alcohol related pancreatitis compared to other etiologies (64% vs 22%, P < 0.05)
Angelini et al[35], 1993, Italy	Prospective cohort	118	Mild: 35 (30%). Severe: 83 (70%)		53	OGTT	-	9 (8)	-	-
Appelros et al[36], 2001, Sweden	Prospective cohort	35	All severe	-	83	Questionnaire, BG, HbA1c	4 (11)	15 (43)	9 (26)	No difference in incidence of diabetes based on etiologies
Malecka-Panas et al[37], 2002, Poland	Prospective cohort	82	Mild: 54 (66%). Severe: 28 (34%)	-	56	OGTT, RIA insulin measurements	2 (2)	15 (16)	6 (7)	-
Ibars et al[17], 2002, Spain	Prospective cohort	55	Mild: 45 (71%). Severe AP 18 (24%)	-	1, 6 and 12	OGTT, arginine test	7 (13)	6 (11)	-	-
Halonen et al[38], 2003, Finland	Prospective cohort	145	All severe	Alcohol: 113 (78%). Others: 32 (22%)	66	Questionnaire	-	68 (47)	-	-
Boreham and Ammori[39], 2003, United Kingdom	Prospective cohort	23	Mild: 16 (70%). Severe: 7 (30%)	-	3	FBG	-	4 (17)	1 (4)	-
Szentkereszty et al[40], 2004, Hungary	Prospective cohort	22	All severe	-	38	Questionnaire	-	3 (14)	-	-
Sabater et al[41], 2004, Spain	Prospective cohort	27	All severe	-	12	Cardinal symptoms identification, 2 basal BG, OGTT in patients with lower BG	-	-	4 (15)	-
Hochman et al[42], 2006, Canada	Prospective cohort	25	All severe	Alcohol: 4 (16%). Biliary: 12 (48%). HTG: 2 (8%). Idiopathic: 7 (28%)	24 and 36	Questionnaire	-	8 (19)	5 (20)	-
Symersky et al[43], 2006, Netherland	Prospective cohort	34	Mild: 22 (65%). Severe: 12 (35%)	-	55	OGTT	-	-	3 (9)	Endocrine insufficiency develops independent of severity of AP
Kaya et al[44], 2007, Turkey	Prospective cohort	112	Mild: 136 (68%). Severe: 63 (32%)	-	12	OGTT	27 (24)	13 (21)	-	No association between endocrine insufficiency and necrosis or disease severity
Yasuda et al[45], 2008, Japan	Prospective cohort	41	All severe	-	56	FBG	-	16 (39)	4 (9)	No difference in etiology, presence of necrosis or alcohol intake among development of diabetes vs no diabetes
Pelli et al[46], 2009, Finland	Prospective cohort	46	Mild: 41 (76%). Severe: 13 (24%)	-	23 (median)	FBG, plasma HbA, OGTT	12 (20.1)	5 (10.8)	-	-
Gupta et al[47], 2009, India	Prospective cohort	30	All severe	Alcohol: 10 (33.3%). Biliary: 12 (40%). Alcohol + biliary 3 (10%). Idiopathic 5 (16.6%)	31	FBG, postprandial sugar level, OGTT, fasting serum C-peptide	6 (20)	6 (20)	6 (100)	No effect of etiology of pancreatitis on the incidence of endocrine insufficiency
Andersson et al[48], 2010, Sweden	Prospective cohort	39	Mild: 26 (65%). Severe: 14 (35%)	-	45	FBG, C-peptide, insulin, OGTT	13 (33)	9 (23)	-	-
Uomo et al[49], 2010, Italy	Prospective cohort	38	All severe	Alcohol 0 (0%). Others: 38 (100%)	179	FBG, OGTT	-	6 (16)	-	No relationship between extent of pancreatic necrosis and endocrine insufficiency
Wu et al[50], 2011 China	Prospective case control	59	Mild: 24 (41%). Severe: 35 (59%)	Gallstone 42 (71%). Hyperlipemia 7 (12%). Alcoholic 7 (12%). Idiopathic 3 (5%)	42	FBG, HbA1c, FBI, C-peptide. HOMA	14 (23.7)	5 (8)	-	Possible risk factors for endocrine dysfunction were pancreatic surgery, pancreatic necrosis, family history of diabetes, obesity, alcohol abuse, smoking and hyperlipidemia
Garip et al[51], 2013, Turkey	Retrospective cohort	96	-	-	32	OGTT	5 (5.2)	33 (43)	-	Severe disease and necrosis was associated with development of new onset diabetes
Vujasinovic et al[52], 2014, Slovenia	Retrospective cohort	100	Mild: 67 (67%). Moderate: 15 (15%). Severe: 18 (18%)	Alcohol: 42 (42%). Biliary: 36 (36%). Idiopathic: 12 (12%). Others: 10 (10%)	32	OGTT, HbA1c	-	14 (14)	-	Severe disease was associated with development of diabetes
Ho et al[53], 2015, Taiwan	Retrospective population-based database study	12284	Mild: 11519 (93.8%). Severe: 665 (6.2%)	Biliary: 6556 (53.3%). Alcohol 5728 (46.7%)	-	ICD-9-CM code for diabetes	-	618 (5)	-	Alcohol associated AP and ≥ 2 admissions for AP were predictors of new onset diabetes mellitus
Chandrasekaran et al[54], 2015, India	Prospective cohort study	35	All severe	Alcohol: 19. Gallstone: 11. Idiopathic: 5	26.6	OGTT	-	17 (48.5)	12 (34.3)	-
Winter Gasparoto et al[55], 2015	Retrospective cohort study	16	-	Biliary: 10 (62.5%). Alcohol: 4 (25.0%). HTG: 2 (12.5%)	34.8	OGTT, C-peptide, HOMA (homeostasis model assessment)	7 (43.7)	5 (31)	-
Yuan et al[56], 2017, China	Retrospective cohort study	310	Mild: 261 (84.19). Moderate: 39 (12.58). Severe: 10 (3.23)	Biliary: 153 (49.35). Hyperlipidemia: 32 (10.32). Alcohol: 15 (4.84). Others: 110 (35.48)	-	FBG	34 (11)	35 (11.3)	-	Hyperlipidemia and fatty liver were predictors of abnormal FBG. Abnormal FBG was not different between alcohol and biliary pancreatitis
Lee et al[8], 2016, Taiwan	Retrospective population-based database study	3187	Mild: 2932 (92%). Severe: 255 (8%)	-	-	ICD-9-CM code for diabetes	-	324	-	-
Umapathy et al[57], 2016, United States	Retrospective cohort study	73	-	-	3 yr (median)			33 (45)		Risk of endocrine insufficiency was associated with extent of necrosis 2/3rd develop diabetes during index admission
Vipperla et al[27], 2016, United States	Retrospective cohort study	101	-	-	34.5	WHO criteria of OGTT	-	28 (28)	-	Risk of diabetes increased with severity of disease
Nikkola et al[58], 2017, Finland	Prospective cohort study	47	-	-	126	FBG, OGTT	13 (27.6)	7 (15)	7 (15)	Pancreatogenic diabetes develops in recurrent AP only
Tu et al[26], 2017, China	Prospective cohort study	113	Mild: 10 (8.8%). Moderate: 12 (10.6%). Severe: 91 (80.6%)	Alcohol: 3 (2.7%). Biliary: 65 (57.5%). Hyper TG: 39 (34.5%). Others 6 (5.3%)	42.9	FBG, OGTT	33 (29.2)	34 (30.1)	-	Extent of pancreatic necrosis > 50%, walled-off necrosis and insulin resistance were independent risk factors for new onset diabetes after AP
Tu et al[25], 2018, China	Prospective cohort study	256	Mild: 54 (21.1%). Moderate: 42 (16.4%). Severe: 160 (62.5%)	Alcohol: 7 (2.7%). Gallstone: 147 (57.5%). Hyperlipemia: 88 (34.5%). Others: 14 (5.3%)	42.9	FBG, OGTT	-	154 (60.2)	-	Incidence of pancreatic necrosis was higher in diabetics (64.7% and 53.0%, P = 0.06). Necrotic debridement (PCD or surgical necrosectomy) were higher in diabetes (66.3% vs 33.7%, P = 0.02)
Phillips et al[59], 2020, United States	Prospective cohort study	186	Mild: 120 (64.5%). Moderate: 40 (21.5%). Severe: 26 (14.0%)	Alcohol: 17 (9.1%). Biliary: 84 (45.2). Idiopathic 26 (16.1%). Post-ERCP 23 (12.4%). Other 17 (9.1%). Hyper TG 15 (8.1%)	12	Questionnaire	-	9 (4.8)	-
Man et al[60], 2022, Romania	Prospective cohort study	329	Mild: 117 (35.6%). Moderate: 167 (50.8%). Severe: 45 (13.7%)	Alcohol: 87 (26.4%). Biliary: 217 (66.7%)	1, 3 and 12 mo	FBG, OGTT, HbA1c	-	29 (8.8)	-	Obesity and pancreatic necrosis > 50% were risk factors for new onset diabetes

AP: Acute pancreatitis; GTT: Gestational trophoblastic tumours; OGTT: Oral glucose tolerance test; BI: Blood insulin; ERCP: Endoscopic retrograde cholangiopancreatography; BG: Blood glucose; HbA1: Hemoglobin A1; HbA1c: Hemoglobin A1c; RIA: Radioimmunoassay; FBG: Fasting blood glucose; HTG: Hypertriglyceridemia; FBI: Fasting blood insulin; HOMA: Homeostatic model assessment; ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification; WHO: World Health Organization; TG: Triglycerides.