Keywords thiamine - bariatric surgery - diabetes
Background
Bariatric surgery is widely used in the treatment of morbid obesity. The benefit extends
to treatment of type 2 diabetes, nonalcoholic fatty liver disease, hypertension, and
dyslipidemia.[1 ] The Swedish Obese Subjects studies showed that bariatric procedures have a long-term
effect and are associated with a significant improvement in quality of life and reduction
in mortality related to cardiovascular disease and cancer.[2 ]
[3 ] In a systemic review and meta-analysis by Park et al, they showed that bariatric
surgery was associated with an increased rate of diabetes remission.[4 ] In obese individuals with type 2 diabetes, bariatric surgery can be associated with
remission of type 2 diabetes in around 80% cases.[2 ]
[3 ] The use of bariatric in type 1 diabetes is associated with decreased weight, improvement
in glycated HbA1c level, and insulin dose reduction (high dose of insulin can be challenging
to be administered in cases of gross obesity).[5 ] Different types of bariatric surgery are used, but the most commonly performed bariatric
surgeries are Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. This involves
resecting part of the stomach and intestine and subsequently repositioning part of
the intestine.[1 ]
[2 ]
[3 ]
[4 ] This can be associated with deficiency of micronutrients, including iron, folate,
vitamin B1 , vitamin B12 , zinc, vitamin D, and calcium.[6 ] Therefore, individuals who have bariatric surgery performed will need dedicated
and specialist nutritional support by dietician and metabolic physician to monitor
and diagnose deficiencies of vitamins, trace elements, and minerals. In this case
report we highlight the important of replacement of thiamine in individuals with diabetes
and bariatric surgery.
Case Presentation
A 29-year-old woman presented with general malaise, abdominal pain, and hyperketonemia.
She has a background of type 1 diabetes, hypothyroidism, and morbid obesity. She was
diagnosed with type 1 diabetes at the age of 4 years. During adolescence, she had
significant weight gain and fatigue which subsequently led to a diagnosis of hypothyroidism.
Six weeks prior to presentation, she had undergone a gastric bypass surgery. Immediately
after the bariatric surgery, she was admitted with severe diabetic ketoacidosis (DKA)
which required intensive treatment unit (ITU) admission. Computed tomography (CT)
scan of the abdomen during admission showed no evidence of postoperative complications
([Fig. 1 ]). After discharge, she notably had significantly and persistently raised ketones:
typically 3 to 5 mmol/L in the morning, which gradually improved during a day. She
lost 16 kg in the 6 weeks following surgery.
Fig. 1 Post gastric bypass computed tomography (CT) abdomen pelvis with contrast, demonstrating
gastrojejunal anastomosis intact following bariatric surgery.
On this admission, she had worsening abdominal pain, limited oral intake, and general
malaise. She reported no focal symptoms of infection. In the days prior to admission,
she had noted that the previous pattern of raised morning ketones had switched to
a pattern of persistent elevation throughout the day. She had continued her regular
basal insulin regime and had adjusted her bolus doses appropriately for her oral intake.
She was taking 8 units of tresiba in the evening, with 1 unit/10 g carbohydrate of
NovaRapid with meals. Aside from insulin, she was only taking 175 µg levothyroxine
once daily. On examination, she was afebrile, with respiratory rate of 16 and regular
comfortable respiratory effort. Her blood pressure was 110/60 and she had a heart
rate of 86. She had a Glasgow Coma Scale (GCS) of 15. Her abdomen was soft and nontender.
On admission, she a capillary blood glucose of 13.3 mmol/L, ketones 4.5 mmol/L, and
pH 7.267. She had a normal inflammatory marker (CRP 9.3 mg/L and WCC of 8 × 109/L)
and normal renal and liver function. She was treated according to the local DKA regimen.
pH, ketone, and glucose improved until they were in the normal range ([Table 1 ], [Fig. 1 ]). However, when she was transitioned onto her regular insulin regime, her ketones
quickly increased again to 3 mmol/L. Empirical, thiamine 50 mg once daily supplementation
began on day 2 of admission. Following starting thiamine supplementation her ketones
remained controlled and remained low (< 0.5 mmol/L) ([Fig. 2 ]). In the subsequent weeks following this admission, we monitored her ketones daily
and noted these remained extremely well controlled (0.01–0.1 mmol/L). She had no further
episodes of ketoacidosis or DKA in the following 4 months. The patient gave consent
for publication of the case report.
Table 1
Improvement in pH (thiamine administration started on day 2)
Day 1 (10 a.m. admission)
Day 1
(1 p.m.)
Day 2
(6 a.m.)
Day 2
(10 p.m.)
Day 3
(3 p.m.)
pH
7.267
7.30
7.34
7.359
7.45
HCO3
20.3
21.3
18.1
20.0
23.0
CO2
6.0
5.5
4.5
4.8
4.5
Na+
135
138
137
134
135
K+
3.8
2.9
3.5
2.77
3.0
Fig. 2 Levels of plasma glucose and ketone before and after thiamine replacement. Importantly,
thiamine replacement (started on day 2) was associated with normalization of plasma
ketones level, and this period is seen in the figure within those black square dots.
Discussion
In this case report, we have shown that thiamine replacement is associated with normalization
of plasma ketones in individuals with type 1 diabetes and bariatric surgery following
an episode of DKA. Importantly, Adnan et al showed that thiamine levels were decreased
in individuals with type 1 and type 2 diabetes and this may be a result of increased
loss of thiamine in urine.[7 ] The main function of thiamine is to act as cofactor of several enzymes important
for carbohydrate (transketolase [TKT], pyruvate dehydrogenase, and α-ketoglutarate
dehydrogenase) and amino acid (branched-chain α-keto acid dehydrogenase) metabolism.[8 ] Therefore, it has been suggested that individuals with diabetes will benefit from
taking thiamine supplement. Importantly, thiamine deficiency can lead to high plasma
ketones level in individuals with type 1 diabetes.[8 ] Interestingly, a clinical trial is in progress to assess whether thiamine replacement
should be part of the protocol of DKA, which is expected to be completed by April
2023.[9 ] The half-life of thiamine is 9 to 18 days and deficiency may result from excess
renal loss or excess alcohol intake. There are two methods for measurement of thiamine
by the laboratory and this may require referral of the sample to the reference laboratory.[8 ] Therefore, we have elected to treat the patient with thiamine rather than wait for
the result from reference laboratory, which may take at least 3 weeks.
Importantly, several reports have shown the association between thiamine deficiency
and bariatric surgery. For instance, Tang et al showed that in cohort of 147 patients
with bariatric surgery 25.7% had thiamine deficiency. Independent risk factors associated
with thiamine deficiency were being African American, a larger preoperative body mass
index (BMI), and self-reported repetitive episodes of nausea and vomiting.[10 ] Malone showed in a review article for data published within 20 years that bariatric
surgery can be associated with thiamine deficiency.[11 ] Different case reports showed that thiamine deficiency can be severe with bariatric
surgery to the extent that patients may present with Wernicke encephalopathy.[12 ]
[13 ]
[14 ]
Importantly, the level of thiamine is also noted to be low in obese individuals with
intention to have bariatric surgery.[15 ]
[16 ] Therefore, it is plausible to suggest that in our patient different factors have
contributed to the need for thiamine replacement; among them are diabetes, obesity,
and bariatric surgery. Ultimately, this may have resulted in persistent high plasma
ketones level since she had the bariatric surgery.