A 35-year-old man diagnosed with type 2 diabetes (T2D) eight years ago and treated with intermittent metformin administration visited our clinic. He had a history of a spontaneously healed ureteral stones ten years ago. He was 169.3 cm tall, weighed 51.6 kg, and his body mass index (BMI) was 18 kg/m2. None of his family members had a known history of diabetes. He complained of a warm and painful lesion on his thigh for the last three weeks, but reported no recent history of trauma or injection. Initial physical examination of the painful lesion revealed tenderness and non-pitting edema of the anteromedial right thigh. His blood pressure and body temperature were 120/80 mmHg and 36.4℃, respectively. There was no leukocytosis (white blood cell count: 9,190/µL) and C-reactive protein was normal, but the erythrocyte sedimentation rate was elevated to 62 mm/hr. His glycemic control was very poor, with an HbA1c 14.5% and postprandial glucose of 446 mg/dL. Other biochemistry values were as follows: serum creatinine 0.4 mg/dL, blood urea nitrogen 24 mg/dL, potassium 4.6 mmol/L, sodium 132 mmol/L, calcium 9.1 mg/dL, phosphorus 3.6 mg/dL, alkaline phosphatase 86 U/L, albumin 4.1 g/dL, and creatinine kinase 436 mg/dL. He had proteinuria (trace) and glycosuria (4+) on urinalysis.
Serial blood culture showed no evidence of bacterial infection. As infectious causes were thought to be less likely, we conducted arterial and venous doppler ultrasonography of the extremity to exclude vascular problems such as deep vein thrombosis or peripheral artery disease. There was no evidence of vascular structural abnormality, but an ill-defined hyperechoic lesion and thick fluid collection in the right vastus medialis muscle was found. After four days, the amount of fluid increased, and thus fluid aspiration at the intermuscular fascial plane adjacent to the vastus lateralis was done (). The fluid was clear, watery and serous. Gram stain and culture of the fluid were negative. Magnetic resonance image (MRI) of the right thigh reflected diffuse edema around the vastus medialis with low signal intensity on T1 () and high signal intensity on T2 images (). The three-phase bone scan showed increased blood flow to the right thigh consistent with myonecrosis as shown on the thigh MRI (). The bone scan also revealed increased blood flow at the right medial tibial condyle consistent with an insufficiency fracture, which was subsequently confirmed by X-ray and MRI (). Since these clinical findings and images were highly suggestive of DMI of the right vastus medialis with insufficient fracture of the right tibial condyle, a muscle biopsy was not performed.
Due to the early onset of disease (age 27), no obesity and no family history of T2D, we needed to clearly identify the exact type of his diabetes. Baseline C-peptide level was very low (0.1 ng/mL) and did not sufficiently rise at 6 min after glucagon stimulation test (0.3 ng/mL). Antinuclear antibodies, and anti-IA2 antibody results were not significant, but antibodies to glutamic acid decarboxylase (anti-GAD Ab) were positive (2.0 U/mL). Other immunologic factors were negative. Considering his age, low BMI, positive anti-GAD Ab, and severely decreased C-peptide level, we diagnosed his diabetes as a case of latent autoimmune diabetes in adults (LADA). After we examined microvascular and macrovascular diabetic complications, he was diagnosed with peripheral neuropathy and non-proliferative retinopathy of both eyes as well as microalbuminuria based on spot urine analysis (152 µg/mg Creatinine).
When we evaluated the cause of the insufficiency fracture, we found that his bone mineral density (BMD) was reduced, with T-scores of -3.9 (Z-score -3.3) at L1-L4 and -2.7 (Z-score -2.3) at the femur neck. Due to the young age of the patient, we also evaluated possible etiologies of secondary osteoporosis, including hyperparathyroidism, hyperthyroidism, hypogonadism, and glucocorticoid excess. 25-hydroxy-vitamin D (25-[OH]D) level was also lower than the normal limits (<4 ng/mL, normal range 11.1 to 42.9) and osteocalcin level was slightly decreased (2.4 ng/mL, normal range 2.7 to 11.5). Thyroid function test was normal (free-T4 0.90 ng/dL, normal range 0.77 to 1.94 ng/dL; Thyroid stimulating hormone 2.24 µU/mL, normal range 0.30 to 4.00 µU/mL; T3 120 ng/dL, normal range 80 to 200 ng/dL), and there was no significant finding of thyroid autoantibodies. Parathyroid hormone (PTH) level was 19.6 pg/mL (normal range 13 to 54 pg/mL). C-telopeptide level was within normal limits (0.74 ng/mL, normal range 0.07 to 0.78 ng/mL). Testosterone and follicle stimulating hormone (FSH) levels were also within normal limits (Testosterone 2.19 ng/mL, normal range, 1.8 to 8.96 ng/mL; FSH 4.0 ng/mL, normal range, 2.8 to 9.6 ng/mL), with a slightly low luteinizing hormone level (1.3 ng/mL, normal range, 1.8 to 5.2 ng/mL).
Antibiotics were initially prescribed, but discontinued when bacterial infection was ruled out and DMI was thought to be the most likely clinical diagnosis. Instead, the patient was treated with analgesics such as acetaminophen, application of a long leg splint and bed rest, and multiple daily injections of insulin for strict glucose control. For his osteoporotic fracture, he was administered oral vitamin D and calcium agents. After about two weeks of supportive management, the tenderness and swelling of the right anteromedial thigh gradually reduced and the patient was able to walk without help, and so the splint was removed. 3 months later, when the hyperglycemia was controlled, we have done the oral glucose tolerance test and calculated the insulinogenic index (IGI, delta insulin 30 min-0 min/delta glucose 30 min-0 min). Calculated IGI was 0 (reference range >0.5), which reflects diminished beta-cell function on glucose stimulation. On follow-up ultrasonography after 6 months, the myonecrosis of the right vastus medialis muscle was dramatically resolved and his HbA1c had improved to 5.7%. In addition, his 25-(OH)D level had risen to 58.7 ng/mL after 6 months of treatment. Five months after treatment, the patient complained of frequent injections, so we changed his insulin regimen to a premixed combination insulin injection twice a day. He is currently under follow-up at the outpatient clinic without any evidence of recurrence.
The formula for computing Cockcroft-Gault is given by CrCl = ((140 - age) * adjusted weight * (gender_coefficient)) / (serum creatinine * 72), where the gender_coefficient is 1 if male, and 0.85 if female. The serum creatinine concentration is in mg/dL.
The patient's gender is male, which means that the gender coefficient is 1.
The patient is 35 years old. 
The concentration of creatinine is 0.4 mg/dL. 
The formula for computing the patient's BMI is (weight)/(height * height), where weight is the patient's weight in kg and height is the patient's height in m.
The patient's height is 169.3 cm, which is 169.3 cm * 1 m / 100 cm = 1.693 m. The patient's weight is 51.6 kg. The patient's bmi is therefore 51.6 kg / (1.693 m * 1.693 m) = 18.003 kg/m^2.The patient's BMI is 18.0, indicating they are underweight.
Because the patient is underweight, we take the patient's weight, 51.6 kg as the patient's adjusted weight needed for the Cockroft-Gault Equation. 
Using the Cockcroft-Gault equation:
CrCl = ((140 - age) * adjusted weight * gender_coefficient) / (serum creatinine * 72).
Plugging the patient's values gives us ((140 - 35) * 51.6 * 1) / (0.4 * 72) = 188.125 mL/min. Hence, the patient's creatinine clearance is 188.125 mL/min.