West Virginia Medical Journal - 2021 - Quarter 2 | Page 40

zyme replacement therapy was initiated . This treatment improved his absorption of fat-soluble vitamins and nutrients to stimulate incretin response , leading to increased insulin release and eventual improved glycemic control . ^{1 , 2 , 4} The next facet of therapy focused on this patient ’ s endocrine deficiency caused by damage to the pancreas via atrophy which was documented on MRI . His hyperglycemia improved quickly with the addition of pancreatic enzymes , which indicated that he still had some intrinsic functioning of his beta cells despite pancreatic atrophy . Given his intact beta cell function , metformin hydrochloride and insulin are first-line agents in this setting ^{1 , 4} and only metformin hydrochloride was initiated , in part , because it decreases gluconeogenesis — a process increased in pancreatic damage due to a decrease in pancreatic polypeptide and a subsequent decrease in insulin receptors on the liver . A secretagogue could have been considered at this stage , ⁴ but glucagon-like peptide 1 ( GLP-1 ) analogues and dipeptidyl peptidase 4 ( DDP-4 ) inhibitors were avoided due to their potential to cause drug-induced pancreatitis . ^{1 , 4} Further , there is not sufficient research evidence to support the use of these medications to improve incretin response .

As the pancreas accrues damage from chronic pancreatitis , insulin therapy will be needed to control this patient ’ s hyperglycemia due to loss of beta cell function . Insulin therapy should be managed in accordance with guidelines set for the management of type 1 diabetes . ² This therapy should be initiated first-line in patients displaying beta cell dysfunction . Non-adherence to this therapy will exacerbate the condition , as demonstrated in our case in which the patient returned to the ED with an even higher HgA1c of 10.1 %. See Table 6 for treatment recommendations . The combination of poor glycemic control and accelerated requirement for insulin suggests that patients with diabetes following pancreatic disease may benefit from management in a specialist setting or with multidisciplinary dietitian and gastroenterology input . ³ This need for increased follow-up is particularly challenging in WV given the large proportion of residents who live in rural areas and must travel long distances to access medical care .

TABLE 3 . Mechanism Comparison of DM1 , DM2 and DM3c

Mechanism DM1 DM2 DM3c beta cell ^{3 , 4}

PP cells ^{3 , 4}

alpha cells ³

intestinal absorption ³

insulin resistance

Decreased insulin production leading to hyperglycemia

Normal PP production

Normal glucagon production

Normal incretin production

Normal / increased insulin production

Normal PP production

Normal / increased glucagon production

Normal incretin production

None Present None

Decreased insulin production leading to hyperglycemia

Decreased PP production leading to decreased hepatic insulin receptors leading to gluconeogenesis and hyperglycemia

Decreased production of glucagon leading to episodes of severe hypoglycemia

Decreased incretin due to decreased absorption of nutrients leading to decreased insulin release and hyperglycemia

DMI : diabetes mellitus type 1 , DM2 : diabetes mellitus type 2 , DM3c : diabetes mellitus type 3c , PP : pancreatic polypeptide

* Superscripts correspond to respective references .

TABLE 4 . Laboratory Features of DM2 and DM3c

Lab Values / Tests DM2 DM3c HgA1c ⁴ Elevated 6.5 % or greater Elevated 6.5 % or greater fasting glucose ⁴ ≥126 mg / dL ≥126 mg / dL

fasting serum insulin level ⁴ Normal / Increased Normal / Low / Absent glucagon ⁴ Normal / Elevated Normal / Low / Absent PP response test ⁴ Normal / Elevated Low / Absent C-peptide ⁴ Normal / Elevated Normal / Low / Absent

incretin secretion ( glucagon – like peptide ( GLP-1 ) or PP or both ¹

Normal Low

DMI : diabetes mellitus type 1 , DM2 : diabetes mellitus type 2 , DM3c : diabetes mellitus type 3c , US : ultrasound , MRI : magnetic resonance imaging , CT : computed tomography

mg / dL : milligram per deciliter * Superscripts correspond to respective references .

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