Risk factors for diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis

Abstract

Introduction: Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as high as 59% over time. However, information on risk factors is limited. We aimed to identify risk factors for developing PD or DM following AP.

Methods: We systematically searched three databases up to 4 September 2023 extracting direct, within-study comparisons of risk factors on the rate of new-onset PD and DM in AP patients. When PD and DM event rates could not be separated, we reported results for this composite outcome as PD/DM. Meta-analysis was performed using the random-effects model to calculate pooled odds ratios (OR) with 95% confidence intervals (CI).

Results: Of the 61 studies identified, 50 were included in the meta-analysis, covering 76,797 participants. The studies reported on 79 risk factors, and meta-analysis was feasible for 34 risk factor and outcome pairs. The odds of developing PD/DM was significantly higher after severe and moderately severe AP (OR: 4.32; CI: 1.76-10.60) than mild AP. Hypertriglyceridemic AP etiology (OR: 3.27; CI: 0.17-63.91) and pancreatic necrosis (OR: 5.53; CI: 1.59-19.21) were associated with a higher risk of developing PD/DM. Alcoholic AP etiology (OR: 1.82; CI: 1.09-3.04), organ failure (OR: 3.19; CI: 0.55-18.64), recurrent AP (OR: 1.89; CI: 0.95-3.77), obesity (OR: 1.85; CI: 1.43-2.38), chronic kidney disease (OR: 2.10; CI: 1.85-2.38), liver cirrhosis (OR: 2.48; CI: 0.18-34.25), and dyslipidemia (OR: 1.82; CI: 0.68-4.84) were associated with a higher risk of developing DM.

Discussion: Severe and moderately severe AP, alcoholic and hypertriglyceridemic etiologies, pancreatic necrosis, organ failure, recurrent acute pancreatitis and comorbidities of obesity, chronic kidney disease liver disease, and dyslipidemia are associated with a higher risk of developing PD or DM.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021281983.

Keywords: acute pancreatitis (AP); diabetes mellitus; gastrointestinal disorders; pancreatitis—complications; prediabetes; risk factor (RF).

Figure 1

PRISMA flow diagram of screened and included studies. PD, Prediabetes; DM, Diabetes mellitus.

Figure 2

Aggregated forest plot summarizing our results for the 34 meta-analyses. Each row shows the pooled odds ratio for a risk factor and outcome pair. An odds ratio over 1.0 indicates that the given outcome (diabetes or PD/DM) is more likely to occur in the exposed group compared to the control group. Statistical significance is achieved if the line of null effect does not fall into the confidence interval. Black squares represent the pooled odds ratios and the lines represent the confidence intervals. PD, Prediabetes; DM, Diabetes mellitus; OR, Odds ratio; CI, Confidence interval; AP, Acute pancreatitis; SAP, Severe acute pancreatitis; MSAP, Moderately severe acute pancreatitis; MAP, Mild acute pancreatitis; HTG, Hypertriglyceridemic; RAP, Recurrent acute pancreatitis; CKD, Chronic kidney disease; and CVD, Cardiovascular disease. ^*Liver disease other than liver cirrhosis.

Figure 3

The association between severity grades of acute pancreatitis (AP) and subsequent development of prediabetes and diabetes. (A) Severe or moderately severe AP vs. mild AP in relation to new-onset prediabetes and diabetes. (B) Severe AP vs. mild or moderately severe AP in relation to new-onset prediabetes and diabetes. (C) Severe or moderately severe AP vs. mild AP and new-onset diabetes. (D) Severe AP vs. mild or moderately severe AP and new-onset diabetes. AP, Acute pancreatitis; OR, Odds ratio; CI, Confidence interval; PD, Prediabetes; DM, Diabetes mellitus; SAP, Severe acute pancreatitis; MSAP, Moderately severe acute pancreatitis; MAP, Mild acute pancreatitis; and vs., versus.

Figure 4

Aggregated forest plot showing the pooled odds ratios for various complications of acute pancreatitis and subsequent diabetes and prediabetes development. PD, Prediabetes; DM, Diabetes mellitus; OR, Odds ratio; and CI, Confidence interval.

Figure 5

Aggregated forest plot showing the pooled odds ratios for different etiologies of acute pancreatitis and new-onset diabetes alone or in combination with prediabetes. Etiologies listed in the exposure column are compared to all other etiologies to provide an odds ratio for the outcome of interest. PD, Prediabetes; DM, Diabetes mellitus; HTG, Hypertriglyceridemic; OR, Odds ratio; and CI, Confidence interval.

Figure 6

The association between recurrent acute pancreatitis and subsequent development of diabetes (A) and prediabetes or diabetes (B). PD, Prediabetes; DM, Diabetes mellitus; OR, Odds ratio; CI, Confidence interval; AP, Acute pancreatitis; and RAP, Recurrent acute pancreatitis.

Figure 7

Aggregated forest plot showing the pooled odds ratios for various comorbidities, demographic factors, and new-onset diabetes alone or in combination with prediabetes. PD, Prediabetes; DM, Diabetes mellitus; OR, Odds ratio; CI, Confidence interval; CKD, Chronic kidney disease; and CVD, Cardiovascular disease. ^*Liver diseases other than liver cirrhosis. ^†Drinking refers to alcohol consumption.