Remission of Type 1 Diabetes with Sitagliptin and Vitamin D

Original Case by Marcelo Maia Pinheiro1, Felipe Moura Maia Pinheiro2 and Margareth Afonso Torres3[1] Pharmaceutical Assistance Center of the State of Mato Grosso, Cuiaba, Brazil[2] Faculdade de Medicina da Universidade de Cuiabá-UNIC, Cuiaba, Brazil [3] Laboratório Clinico do Hospital Israelita Albert Eistein, São Paulo, SP, Brazil

Patient #1 was a 20-year-old woman with a history of hypothyroidism due to Hashimoto’s thyroiditis treated since the age of 6 years with levothyroxine. In April 2012, she presented with weight loss, polyuria, polydipsia and leg cramps. Her physical examination was normal; she weighed 62 kg, had a body mass index (BMI) of 21.7 kg/m2 and blood pressure of 100/60 mmHg. She had a grandmother with Hashimoto’s thyroiditis and type 2 diabetes mellitus.

Q What percentage of type 1 diabetic have autoimmune thyroid disorder ?

  • 2-5% have overt hypothyroidism
  • 20% have Anti TPO positive

Q What is the effect of subclinical hypothyroidism in type 1 diabetes ?

  • Reduced linear growth
  • Increased risk of Hypoglycemia

Q How and when if TFT monitoring done in children with type 1 diabetes ?

  • At the time of diagnosis
  • If normal repeat every 1-2 years

Q What percentage of type 1 diabetics have celiac disease ?

  • 5%

Q What are concerns with celiac disease in type 1  ?

  • Risk of hypoglycemia
  • Poor linear growth
  • Poor bone accural

Q How is screening for celiac done in type 1 diabetics ?

  • At the time of diagnosis
  • Every 1-2 years after diagnosis
  • Use Anti TTG antibody – if positive then do Duodenal biopsy

Q Which HLA in type 1 has higher risk of autoimmune disease ?

  • HLA DR3 > HLA DR4

Q Enlist some other autoimmune disorder in type 1 diabetes ?

  • Autoimmune adrenalitis
  • APS type 2
  • IPEX syndrome

Patient #2 was a 21-year-old woman who presented in May 2011 with weight loss, polyuria, polydipsia and leg cramps. Her physical examination was normal; she weighed 62.5 kg, had a BMI of 19.5 kg/m2 and blood pressure of 115/70 mmHg. Her mother had Hashimoto’s thyroiditis, and her brother had Crohn’s disease

The diagnosis of diabetes mellitus was confirmed in patient #1 based on her serum glucose and HbA1c levels (Fig. 1 and Table 1). The patient’s anti-GAD antibody was positive (Fig. 2)

Q Enlist the antibodies associated with type 1 diabetes ?

  • GAD 65
  • Insulinoma associated antibody – IA-2 (also called ICA5-12)
  • Insulin autoantibody – IAA
  • Zinc transporter 8 antibody- Znt8

Q Antibodies are formed against which part of GAD65 ?

  • Carboxy terminal of GAD65 antibody

Q What is the other name of Insulinoma associated antibody 2  ?

  • ICA512

Q Tell me something about GAD65 antibody ?

  • Present in 70% of type 1 diabetics
  • Does not reduce with age- most common antibody to check in adults
  • Slowly developing diabetes
  • HLA-DR3 associated

Q Which is the antigenic main target in type 1 diabetes ?

  • The main target seems to be Beta chain of Insulin

Q Which is the first antibody to appear in type 1 diabetes  ?

  • IAA- insulin autoantibody is the first to appear

Q  If IAA is the first to appear, why does it not have more importance compared to GAD65 etc  ?

  • Any person given insulin can develop IAA antibody
  • Hence measurement of antibody anytime after 2 weeks after insulin injection will give a positive result

Q Which is often the last antibody to appear ?

  • Znt8
  • It disappears also first
  • IAA first à then GAD à then IA2 à Last ZnT8

Q Summarize the prevelance of various antibodies in type 1 diabetes ?

  • IAA – almost 100% – but not reliable marker
  • GAD65- 70%
  • IA-2 – 68%
  • Znt8 – 60-80%

Q What do Indian studies say about Antibodies in type 1 ?

  • South Indian study – GAD65 was present in 70% – just like west
  • Cuttuck Study- ICA512 was more common – in 43% , GAD65 only in 7%
  • Her HLA typing was DQA1*01:01, 03:01, DQB1*03:02, 05:01, DRB1*04:01, 10:01. Of note, the occurrence of the haplotype HLA-DQA1*03:01, −DQB1*03:02, −DRB1*04:01 is associated with an increased risk of T1DM.

Q What is the role of MHC ?

  • MHC carry the antigen on the surface of antigen presenting cells and activate the T cells

Q Which 2 haplotypes of HLA  confer the highest risk of type 1 diabetes ?

  • HLA DR3,DQB1*0201 – Also called HLA DR3- DQ2
  • HLA DR4,DQB1*0302 – also called HLA DR4-DQ8
  • 90% of type 1 have either of these two haplotypes
  • 30% have both !
  • The risk of type 1 diabetes is you carry either of these two haplotypes is 5% compared to 0.4 % in controls

Q Which HLA haplotypes protect from type 1 ?

  • HLADRB1*0403
  • HLADPB1*0402
  • Additionally HLA DQB1*0602 – also protective

In patient #2, the diagnosis of diabetes mellitus was also confirmed by serum glucose and HbA1c levels (Fig. 1 and Table 1). The patient’s anti-GAD antibody was positive (Fig. 2), her urinalysis revealed glycosuria without ketonuria, and her serum levels of lipids, BUN and creatinine were normal. Antithyroid antibodies measurement (Table 1) and thyroid ultrasound evaluation confirmed the diagnosis of Hashimoto’s thyroiditis with a normal TSH level (1.83 µIU/mL). Her HLA typing was DQA1*01:01, 01:01, DQB1*05:01, 05:01, DRB1*01:01, 01:01, which is not associated with an increased risk of T1DM.

Q How will you treat these patients ?

  • I would start both the patients on Basal-bolus insulin regimen.
  • I would start with 0.5 unit/kg of total insulin dose with 50% basal and 50% bolus.
  • I would also screen these patients for Celiac disease at baseline.

Patient #1 started treatment with insulin glargine 35 IU once a day and insulin lispro 2 IU before breakfast and 6 IU before lunch and dinner.

On May 2012, she started treatment with sitagliptin 100 mg/day and vitamin D3 5000 IU/day, and on June 6, 2012, she interrupted the administration of insulin.

Patient #2 started treatment with insulin glargine 20 IU once a day, and insulin glulisine 6 IU before breakfast, lunch and dinner. In July 2011, she experienced a honeymoon phase in which she used only insulin glargine 6–10 IU/day. Two months later, she resumed a basal-bolus regimen with the same initial doses. In March 2012, she was started on sitagliptin 100 mg/day and vitamin D3 5000 IU/day.

Both patients were duly informed that treatment of T1DM with sitagliptin and vitamin D3 was off-label and signed an informed consent form, accepting this treatment.

Q What is the objective definition of Honeymoon phase of Type 1 diabetes ?

  • Partial remission of honeymoon phase of type 1 diabetes is defined as follows:
  • HbA1c <6.0%
  • Insulin requirement
  • Stimulated C peptide >0.9 ng/ml

Q How long does the honeymoon phase last ?

  • It lasts for several weeks to months. It rarely lasts beyond 1 year.

Q What is the recommended dose of Vitamin D daily in adults ?

  • Recommended Daily allowance of Vitamin D is 600 IU /day
  • For those having Vitamin D deficiency, it is recommended to give 60,000 IU once a week for 8 weeks followed by 2000 IU once a day.

Patient #1 continues treatment with sitagliptin and vitamin D3. Since June 6, 2012, she has not used insulin and her levels of capillary glucose and serum fasting glucose, HbA1c and C-peptide remain normal (Fig. 1). In May 2014, her glucose levels, determined with a continuous glucose monitoring system (CGMS-72 h), confirmed the persistence of normal glucose values (Fig. 2).

Q Patient #1 has vitamin D levels of 22 ng/ml. According to Endocrine society guidelines, how will you classify her Vitamin D status ?

  • Vitamin D values between 20-29 ng/ml are classified as Vitamin D insufficiency.

Q How will you convert Vitamin D ng/ml to nmol/l ?

  • Vitamin D value of 1 ng/ml is 0.4 nmol/l

After 1 month of treatment with sitagliptin and vitamin D3, patient #2 started decreasing her insulin dose, and in March 2015, she interrupted the administration of insulin glargine. At the time of this report, she was only administering insulin glulisine 2–4 IU before breakfast, lunch and dinner when eating carbohydrates and she maintains use of sitagliptin and vitamin D3. She chose not to interrupt the use of insulin glulisine to maintain flexibility in her diet. She has been maintaining normal levels of capillary glucose, fasting blood glucose, HbA1c and C-peptide (Fig. 1). Results from her CGMS-72 h in May 2014 were normal (Fig. 2).

Both patients maintained normal serum levels of calcium and 25(OH) vitamin D. No side effects related to sitagliptin use have been reported by the patients.

Q Where does the evidence of vitamin D action in type 1 diabetes come from ?

  • Mainly from observation studies which have shown that vitamin D deficiency is associated with increased risk of diabetes

Case control studies have shown that vitamin D reduces risk of type 1 diabetes by 30%

  • However there are no RCT for use of vitamin D in type 1 diabetes
  • Genetic polymorphism in vitamin D has been associated with diabetes

Q How does vitamin D reduce risk of type 1 diabetes ?

  • Immune modulation
  • Increase insulin secretion (see later)
  • Reduce beta cell apoptosis

Q How does vitamin D reduce beta cell apoptosis ?

  • Vitamin D activates- Nf- kb pathway which increase beta cell survival

Q What kind of immune modulation is seen with vitamin D which is beneficial for type 1 diabetes ?

  • Its actions mainly via 1,25 Dihydroxyvitamin D produced by the macrophages
  • Reduces Th1
  • Increases Th2
  • Reduces production of IgG by B cells
  • Increases Treg (Regulatory T cells) cell function
  • Reduce damaging cytokine production

Q What are the potential benefits of Sitagliptin in Type 1 diabetes ?

  • By its incretin effect Sitagliptin can increase the GLP1, which can potentially enhance beta cell survival and function
  • Sitagliptin may potentially have immunomodulatory effects in Type 1 diabetes.

Q What is the effect of Sitagliptin on Immune system relevant to type 1 diabetes ?

  • Sitagliptin is shown to reduce Th1 cytokine (IFN –gamma) and increase Th2 Cytokine (IL-4)

Q What is the effect of DPP IV inhibitors in type 1 diabetes ?

  • Meta-analysis by Guo et al shows that DPP IV use in type 1 diabetes reduces the insulin dose requirement without change in HbA1c.
  • It does not increase or reduce the risk of hypoglycemia.

Q Apart from this case, has it been shown before that DPP IV inhibitors can potentially reverse type 1 diabetes ?

  • In several studies in NOD mice which are models for type 1 diabetes it has been shown that DPP IV can delay the onset of type 1 diabetes or bring an early onset type 1 diabetes in remission.

Learning Objectives

  1. DPP IV inhibitors and Vitamin D have immunomodulatory effects which can potentially reverse and early onset type 1 diabetes and bring it to remission.
  2. Partial remission of type 1 diabetes (Honeymoon phase) is defined as Insulin requirement 0.9 ng/ml.


Original Case by Satoshi Yamagata et al

An 81-year-old male had experienced vomiting, dizziness, and appetite loss for 2 weeks. There had not been recognition of diabetes prior to the onset of this illness. On admission, he showed impaired consciousness (Glasgow Coma Scale score, 12) with no neurologically abnormal findings or abdominal tenderness. However, he had a dry tongue and decreased skin turgor. His height was 158 cm, body weight 42.1 kg, and body mass index 16.7 kg/m2. His blood pressure was 138/78 mm Hg with an irregular pulse and heartbeat. His body temperature was 35.8°C. Electrocardiography revealed atrial fibrillation. He had no familial history of diabetes. There was no history of falling or bruising.

Q Which endocrine condition would you suspect here ?

Clinically I would suspect Thyrotoxicosis from this history. Points in favour are

  1. Low BMI
  2. Atrial fibrillation
  3. Loss of appetite- Apathetic thyrotoxicosis in elderly

Biochemical analysis revealed high levels of serum 3-hydroxybutyrate (6,296 μmol/L) and the presence of urine ketones and metabolic acidosis, which suggested DKA. His plasma glucose level and glycated hemoglobin level were 732 mg/dL (40.6 mmol/L) and 6.9% (56 nmol/mol), respectively. Urinary C-peptide excretion was <0.1 μg/day, and serum C-peptide level was <0.1 ng/mL after intravenous glucagon loading at onset.  Table 1

Q What is the interpretation of Glucagon stimulation test ?

C peptide 6 min after 1 mg of Glucagon, if the value is <1.8 ng/ml it is considered to be low.

Q What is your interpretation from the biochemical investigations ?

  1. The high blood sugar, low C peptide and presence of ketoacidosis go in favour of absolute insulin deficiency.
  2. Absence of GAD 65 and IA2 antibody go against the possibility of autoimmune etiology. However, presence of other antibodies cannot be ruled out.
  3. The low calcium and increase phosphorous are suspicious. I would consider going a vitamin D and PTH. Also the alkaline phosphatase is high
  4. Amylase is high. I would do a pancreatic imaging.
  5. The increase CPK gives a hint of Rhabdomyolysis
  6. As you can see from the chart, there is multiple organ involvement. A possibility of multi system involvement must be kept in mind

Q The high blood sugar with a low HbA1c suggests what ?

It suggests a possibility of Fulminant type 1 diabetes

Q What is Fulminant type 1 Diabetes ?

It is a severe form of diabetes in which rapid destruction of pancreatic beta cell occurs within no time leading to absolute insulin resistance.

Q What are the clinical characteristics of Fulminant Type 1 Diabetes ?

  1. Abrupt onset of action
  2. Negligible C peptide at onset
  3. Negative islet associated antibodies
  4. Ketoacidosis at onset
  5. Relatively short history of symptoms- <1 week
  6. Elevated pancreatic enzymes

It is described predominantly in Japan

Laboratory data on admission showed high concentrations of serum creatine kinase (CK) (31,084 U/L), myoglobin (122,335 ng/mL), and myoglobinuria, which indicated the onset of rhabdomyolysis. Blood urea nitrogen and serum creatinine (Cr) were both increased (101 mg/dL and 3.6 mg/dL, respectively), and the plasma osmolality level was high (370 mOsm/kg H2O). Glutamic acid decarboxylase and insulinoma-associated antigen 2 antibodies were undetectable.

Q Which are the important antibodies in Type 1 Diabetes ?

  1. Anti GAD65 antibody
  2. Anti Insulinoma associated antibody 2
  3. Anti Insulin autoantibody
  4. Anti Znt8

Thyroid hormones were within normal ranges: free triiodothyronine, 2.62 pg/mL; free thyroxine, 0.90 ng/dL; thyroid-stimulating hormone, 2.08 μIU/mL. The following serological markers for viruses were all negative: coxsackie A9, B2, B4, and B5; cytomegalo; mumps; herpes 6; Epstein-Barr; influenza; herpes simplex; echo 1, 3, and 7; varicella zoster; and rubella. A drug screen performed by Triage® DOA (Biosite Diagnostics Inc, San Diego, CA) was negative.

We treated the patient with 4,000 mL/24 hour saline and continuous venous insulin infusion on the first day (Fig. 1). Empiric broad-spectrum antibiotics were administered for a urinary tract infection. Blood glucose and pH levels normalized 1 day after treatment. However, he was treated with continuous hemodiafiltration on the second day because of anuria and elevated serum CK concentrations (78,225 U/L). Although his serum CK concentrations improved to within the normal range 1 week after treatment, daily urinary volume remained decreased (<50–100 mL/day).

HD was introduced on hospital day 10. After 16 HD sessions, his serum Cr concentrations transiently increased to 12.5 mg/dL and then decreased to 6 mg/dL. Daily urinary volumes gradually increased to >1,500 mL/day. Finally, HD was completed 46 days after starting continuous hemodiafiltration (CHDF). Two weeks after the final HD, his serum Cr concentrations had improved to 2.0 mg/dL

Q Is there a link between Rhabdomyolysis and DKA ?

Yes. Rhabdomyolysis may be associated with DKA.

Learning points from this case

  1. Fulminant Type 1 diabetes is an antibody negative type 1 diabetes which presents rapidly with diabetic ketoacidosis
  2. Rhabdomyolysis may be associated with diabetes ketoacidosis .


Original case Soham Mukherjee et al

A 42-year-old female patient presented with complaint of pain and swelling in the right calf for the last 2 months (Fig. 1a). There was no history of fever. She was a known case of type 2 diabetes mellitus (T2DM) for the last 11 years, hypertensive for the last 1 year and hypothyroidism for the last 2 months. Patient underwent hysterectomy 3 years back. There was no history of trauma, i.m. injection, arthralgia or other systemic symptoms.

Q What would you suspect when a diabetic patient presents with history of pain and swelling of calf muscles ?

My differential diagnosis would be

  1. Cellulitis
  2. Deep vein thrombosis
  3. Lymphedema
  4. Baker’s cyst
  5. Calf muscle tear
  6. Venous valvular insufficiency.
  7. Diabetic myonecrosis

On examination, right leg was swollen, tender and indurated.

Q What investigation would you order ?

  1. Compression ultrasonography of the lower limb (venous doppler with compression)
  2. D-Dimer

Q  Is diabetes a risk factor for DVT ?

It is controversial. Diabetes per se is not a risk factor for DVT. In a study conducted by Heit et al ,they found incidence of DVT in diabetics no different from general population.

On evaluation, patient had all microvascular complications of diabetes.

  1. What is the importance of knowing that this patient has other diabetic microvascular complications in this case ?
  2. Presence of other microvascular complications increases the risk of patient have diabetic foot with cellulitis
  3. Diabetic myonecrosis is also considered a vascular complication of diabetes and presence of other microvascular complications increases the likelihood of patient having diabetic myonecrosis.

Investigation revealed hemoglobin of 7 g/dl (11–15 mg/dl), total leucocyte count 10 200/mm3 (4000–11 000/mm3), platelets 293×103/mm3, peripheral blood film suggestive of microcytic hypochromic red blood cell, urea 72 mg/dl (10–50 mg/dl), creatinine 3.2 mg/dl (0.5–1.2 mg/dl), HbA1c 8% (3.8–5.6%), thyroid-stimulating hormone (TSH) 10.8 μIU/ml (0.27–4.2 μIU/ml), thyroxine (T4) 6.98 μg/dl (4.8–12.7 μg/dl), tri-iodothyronine (T3) 0.8 ng/ml (0.8–2.0 ng/ml), 24 h urinary protein 550 mg/day and CK 403.5 U/l (26–308 U/l). ANA, ANCA, RA factor, dsDNA, SSA/RO, SSB/LA, Sm, Sm/RNP, Scl70, Jo1 were negative and coagulation profile was normal.

  1. What other condition in this patient could have led to myalgia and raised CK levels ?


Fundus examination revealed hard exudates. Blood culture was sterile. Deep vein thrombosis (DVT) was excluded by compression ultrasonogram (USG).

Q What would you consider next ?

Since the diagnosis is still not clear, I would advise and MRI of the limb.

USG of the right leg was suggestive of diffuse thickening and increased echogenicity of skin and subcutaneous tissue along with marked swelling and hypoechogenicity of muscles without any localized collection. MRI right leg revealed thickening and edema of the skin/subcutaneous tissue with hyperintensity in muscles of all the compartments of the right leg in short tau inversion recovery (STIR) sequence (Fig. 1b and c). Electromyography (EMG) was suggestive of inflammatory myositis. Muscle biopsy (Fig. 1d) from right gastrocnemius was performed as calf muscle involvement is relatively uncommon in Diabetes myonecrosis. Patient was diagnosed to have Diabetes myonecrosis and was treated conservatively with paracetamol and tramadol with complete recovery within 6 weeks. The dose of levothyroxine was also optimized.


Q What is diabetic myonecrosis ?

It is spontaneous infarction of muscles in diabetic patients which is unrelated to atheroembolism or occlusion of any major arteries.

Q It is common in what type of diabetics ?

It is more common in long standing uncontrolled diabetics.  It is more common in type 1 diabetics.

Q Which muscles are commonly involved in this conditions ?

Muscles of thigh and calf are commonly involved. Quadriceps muscle is most commonly involved. It may present acutely and the involved muscle may be tender. Patient may run mild fever. The condition tends to recur after resolution.

Q Is the creatinine kinase elevated in these patients ?

As seen in this case CK may be elevated but only mildly in patients with Diabetic myonecrosis.

Q What does MRI in such cases show ?

  1. High signal intensity in T2W image in the involved muscles
  2. Post gadolinium contrast there is patchy enhancement of the involved muscles. While the infarcted muscle shows no enhancement , the surrounding edema and inflammation shows reasonable enhancement.
  3. Loss of fatty intermuscular septae

Q What is the treatment of diabetic myonecrosis ?

Treatment is mainly conservative with rest and NSAIDS. It spontaneously resolves in a few weeks.


Original case : Alejandra Borensztein et al. (AACE Case reports)

A 58 year-old male with hypertension and rheumatoid arthritis presented with weakness, blurred vision, polydipsia, and polyuria for 1 week and shaking of the left leg for 4 days. He also complained of poor appetite, nausea, and vomiting. The neurologic examination revealed normal motor tone and strength. Deep tendon reflexes were reduced throughout, and Babinski reflexes were plantar bilaterally. He had nonsuppressible episodes of rhythmic, clonic jerking of the left leg that consisted of simultaneous partial flexion of the hip and knee and dorsiflexion of the foot. These movements occurred spontaneously as well as in response to provocation (i.e., forced plantar flexion, pressure). Although the patient was ambulatory, these movements would at times interfere with his activities. The rest of the physical exam was unremarkable.

Q Can movement disorder be presenting complaint of diabetes ?


Q In which patients with diabetes are movement disorders commonly seen ?

They are more common in patients with Hyperosmolar hyperglycemia state (HHS). It is more common in elderly women with uncontrolled diabetes.

Q Is the chorea seen with HHS reversible ?

Yes. It often reverses with the correction of hyperglycemia

Q What is the characteristic Neuroimaging picture seen in studies in patients with movement disorder and diabetes ?

Hyperdensity in putamen/caudate lobe are common in patients with Diabetes and movement disorder

Q Which other endocrinal conditions presents with Movement disorders ?

  1. Hypoparathyroidism, Pseudohypoparathyroidism and Fahr’s disease on account on basal ganglia calcification can present with abnormal movements and Parkinson like features
  2. Hypothyroidism can be mistaken for Parkinsonism
  3. Hyperthyroidism can present with chorea
  4. Hashimoto’s encephalitis can also present with chorea
  5. Hypoglycemia is a cause of chorea
  6. Hyperthyroidism is associated with fine tremors

The serum glucose was 891 mg/dL (65–115 mg/dL), and calculated serum osmolality was 313 mOsm/kg (285–295 mOsm/kg). Other pertinent admission data can be found in Table 1.

Q What is your conclusion from these lab reports ?

We are probably dealing with a case of Hyperglycemic hyperosmolar state.
Q What is the diagnostic criteria for HHS ?

  1. Blood glucose >600 mg/dl
  2. Serum osmolality >320 mosm/kg
  3. Absence of significant ketosis

The neurology consultant made a presumptive diagnosis of Epilepsia Partialis continua. He was treated with aggressive intravenous hydration and an insulin drip.

Q Summarize the management of HHS ?


  1. 1 litre of 0.9% Normal saline is given over 1 hr
  2. Reassess the fluid status
    1. If patient in hypovoluemic shock – 1 litre of NS every hour till blood pressure improves
    2. If patient not in shock see below
  3. Patient not in shock- check the Serum sodium
    1. Hypernatremia/Normal sodium- give 0.45% Saline @10 ml/kg/hr
    2. Hyponatremia- give 0.9% Saline @10ml/kg/hr
  4. This is continued till blood glucose <300 mg/dl – then start 0.45% + Dextrose @100-200 ml/hr


  1. 15 units/kg IV stat followed by
  2. 1 units/kg/hr till blood glucose <300 mg/dl
  3. Double the rate of insfusion if the blood sugar doesn’t fall by >50 mg/dl/hr
  4. Once blood glucose <300 mg/dl- then reduce the rate to half and maintain the blood glucose in range of around 250 mg/dl


  • If K < 3.3 meq/l
    • donot give insulin
    • 2 ampules of 11.2% KCl in 500ml of NS @200ml/hr
  • If K – 3.3- 5 meq/l
    • Can start insulin
    • 1 ampule of 11.2% KCl in 500ml of NS@ 200ml/hr
  • If K >5.0 – don’t give insulin
  • Ideally must be given as a mixture of 2/3rd of KCl and 1/3rd KPO4
  • 20-30 meq of K in 1 litre of fluid is generally adequate

On the second day, his glucose decreased to the 189 mg/dL. An electroencephalogram performed that day showed diffuse cerebral dysfunction without an epileptogenic focus. After glucose normalization, the abnormal movements disappeared and did not recur. Magnetic resonance imaging (MRI) performed 1 month later revealed diffuse periventricular microvascular changes without focal abnormality


Case 2

A 77 year-old male with type 2 diabetes and pancreatic cancer metastatic to the peritoneum presented to the emergency department with a 1-week history of uncontrollable jerking movements of his left arm. The movements were nonsuppressible, and according to the patient, appeared to worsen in concordance with an increase in his glucose finger stick values. He also complained of polydipsia, polyuria, nocturia, nausea, and sweating.

The neurological examination was remarkable for mild dysdiadochokinesia (an inability to perform rapid alternating movements) and a coarse, regular, 2–3/second, action-induced tremor at the left elbow, wrist, and fingers. These movements were not present at rest. The jerking disrupted voluntary repetitive movements and persisted on attempted relaxation, consistent with a rubral tremor. The initial laboratory evaluation showed a glucose level of 577 mg/dL (65–115 mg/dL) and calculated serum osmolality of 294 mOsm/kg (285–295 mOsm/kg). Additional clinical and laboratory data can be found in Table 1. Brain computed tomography showed a trace periventricular hypodensity without mass effect, suggestive of chronic microvascular disease.

He was started on insulin, with normalization of the blood glucose level by the second day. MRI performed on day 2 of admission showed mild chronic microvascular change without focal lesions. Repeat neurologic evaluation on day 2 revealed complete resolution of all abnormal movements; these did not recur during follow-up.



Q Which is the most common movement disorder in diabetics (Hyperglycemia induced involuntary movement- HIIM) ?

Hemichorea-hemiballismus is the most common .

Q What is the theory which explains HIIM ?

  1. Hyperglycemia causes a Shift away from Kreb’s cycle to anerobic pathway. This causes depletion of GABA in CNS leading to increase of seizure threshold.
  2. Hyperglycemia can produce reduction in regional blood flow that can lead to reversible ischemia
  3. HHS can lead to increase viscosity of the blood which can lead to reversible ischemic state

Learning points from this case

  1. Hyperglycemia (especially HHS) can be associated with hyperkinetic movement disorder. Hemichorea-Hemiballismus is the most common movement disorder in such patients.
  2. The entity is known as ‘Hyperglycemia Induced involuntary movements’ which is often reversed completely by control of hyperglycemia.