CME INDIA Presentation by Dr. Mahadev Desai, Senior Consultant Physician at HCG Multispecialty Hospital, Ahmedabad. Served as Teaching Faculty in various Medical Colleges of Gujarat. Served as Honorary Editor of Gujarat Medical Journal.

A Real-Life Scenario.

One of my real-life cases

  • I wish to describe one of my real-life cases, who is a 59-year female, my long-time patient of Hypertension and Hypothyroidism, Allergic bronchitis requiring intermittent steroid in past.
  • She did not have diabetes or hyperglycemia in past. She had Covid19 infection in November 2020 managed at home. She did not receive steroids during the treatment at home.
  • I examined her on 31/03/2021 for c/o fatigue and weight loss of about 4.5 kg in 4 months.

Physical examination did not reveal any abnormality except tachycardia.

  • Her ECG showed Sinus tachycardia, LAD and LBBB (Earlier ECG showed only LVH and LAD. She was immediately referred to Cardiologist in view of above findings and all investigations including Troponin T were sent.
  • Her 2D echocardiogram showed LVEF of 45% and LVH but no RWMA or PAH. Coronary Angiography was planned awaiting all reports.
  • Troponin levels were within normal limits and repeat ECG after 2 hours did not show any changes from the earlier one.

To my utter surprise her random blood glucose was 802 mg/dL, HbA1c was 16.2%

  • Even on retrospective interrogation she only came out with c/o mild polydipsia and mild increase in frequency of urination. She was immediately advised hospitalization, where her blood glucose on glucometer was HH.
  • She was started with Insulin Infusion 5 units of rapid acting human insulin and normal saline infusion of 100 mL/hour. Over next 6 hours her plasma glucose decreased to 475 mg, 322 mg, 250 mg and 160 mg with variable rate intravenous insulin infusion (VRIII).
  • Her serum acetone, S. electrolytes, renal and liver functions reports, S. Amylase and S. lipase were within normal limits except mildly lower S. Potassium levels. She was also started with KCl infusion. Her ECG showed disappearance of LBBB and regaining of her earlier ECG findings. Over next two days her plasma glucose could be brought under 250 mg.
  •  She was started with basal Glargine insulin and Tab. Metformin and Repaglinide. She was discharged on day 7 with Once-a-day Glargine insulin (16 units) and same oral drugs.
  • Her thyroxine dose was reduced as her reports showed increase in T4 and very low level of TSH (Initially I thought it as one of the contributing causes for weight loss).

She did not have symptoms of severe hyperglycemia

  • Even on repeated questioning she denied symptoms other than weight loss and mild polydipsia and polyuria.
  • New Onset Diabetes (NOD) or unmasking of pre-existing diabetes or progression of prediabetes to overt diabetes are all reported and factors like use of steroids, stress, sepsis, involvement of pancreas are possible contributory factors.

Silent” or “happy” hyperglycemia of Long Covid

  • Can we consider this a case of “silent” or “happy” (of course there is nothing to be happy about) hyperglycemia of Long Covid because her HbA1c was 16.2% indicating persistent hyperglycemia of past few months coinciding with her Covid19 illness for which she had hardly any symptoms or signs? (Whatever s/s she presented were clearly disproportionate to her degree of hyperglycemia)?

CME INDIA Learning Points

  • There is increasing evidence that COVID-19 may lead to new-onset diabetes mellitus (DM).
  • This may occur even in patients without predisposing factors for impaired glucose metabolism.
  • It is worth to note that new-onset hyperglycaemia is associated with worse prognosis in patients with COVID-19. Its prognosis may be even more sinister than in patients with pre-existing DM.
  • Acute DM has been commonly observed in individuals with no history of DM or glucocorticoid use, and was an independent predictor of mortality “New-onset” hyperglycaemia and acute metabolic decompensation of pre-existing DM are now emerging as a complication of COVID-19, especially among hospitalised patients. Impressively, this “new-onset” hyperglycaemia is not associated with any other risk factors, notably obesity, prediabetes, DM, or corticosteroid administration. These findings point to a bidirectional relationship between DM and COVID-19
  • COVID-19 may accelerate diabetic ketoacidosis (DKA) in subjects with new-onset or pre-existing DM
  • Both impaired pancreatic insulin secretion and insulin resistance have been implicated as underlying mechanisms. SARS-CoV-2 may enter the pancreatic beta cells via the expression of angiotensin-converting enzyme 2 (ACE2) receptors It would be possible that the virus impairs pancreatic insulin secretion, thereby either aggravating DM or triggering new-onset DM
  • Another mechanism appears to be insulin resistance due to the high levels of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα) in subjects with severe COVID-19  
  • We need to deal with the emerging clinical implications, mastering the “fearful symmetry” of new dragon.

CME INDIA View Points

The presentations do not fit two types of diabetes exactly

  • What is confusing about these cases is sometimes they look like ‘classic’ type 1 or type 2 diabetes, but on other occasions, the presentations do not fit those two types exactly. The question has become, is this a new form of diabetes? Is it really due to a loss of insulin or hepatic glucose production, or both? Then, there have been reports that COVID-19 infection induces hyperglycemia in many individuals.” – Mark Atkinson, PhD, the Jeffrey Keene Family Professor at the University of Florida and director of the University of Florida Diabetes

Registry could be the Answer

  • There is clearly a bidirectional relationship between diabetes and COVID-19, but it remains to be seen whether COVID-19 can actually cause new diabetes, and that is what we set out to investigate with a registry,”

Learning from case reports

  • Global registry for COVID-19-related diabetes cases is a joint initiative with King’s College London and Monash University, is designed to establish the extent and characteristics of new-onset, COVID-19-related diabetes and investigate its pathogenesis, management and outcomes.
  •  “We anticipate that many ‘new-onset diabetes’ cases that we find might actually be preexisting diabetes. Or perhaps a minority will truly be new-onset, but by calling on the entire world to contribute, we hope to gather a large sample Reference”- Rubino s
  • COVIDIAB registry. Available at: https://covidiab.e-dendrite.com. Accessed March 19, 2021.

What does seem clear

  • SARS-CoV-2 infection, like many other infections, has the ability to induce hyperglycemia in people without a previous diagnosis of diabetes, be it through diminished insulin secretion, enhanced release of counter-regulatory hormones, excessive hepatic glucose production, impaired glucose disposal, or a combination of these factors.

Why Questions?

  • Diabetes onset has been noted, in case reports, to occur simultaneously with acute SARS-CoV-2 infection or in the weeks to months following recovery from the infection.
  • But, findings from epidemiological studies have been conflicting: for example, work from the UK showed an increase in type 1 diabetes incidence during the COVID-19 pandemic, whereas a larger study from Germany showed no such change
  • No study has confirmed COVID-19 diagnosis or accounted for viral load as a potential contributing factor.
  • The potential role of SARS-CoV-2 in inducing diabetes is likely to be more complex than the mere notion of pancreatic ACE2 expression and β-cell destruction.

CME INDIA Tail Piece

Hyperglycemia - Long Covid

References:

  1. Mark A Atkinson,Alvin C Powers.Distinguishing the real from the hyperglycaemia: does COVID-19 induce diabetesPublished: April 07, 2021
  2. https://www.healio.com/news/endocrinology/20210320/evidence-conflicting-on-covid19-as-cause-of-newonset-diabetes
  3. Stella Papachristou et al.New-Onset Diabetes in COVID-19: Time to Frame Its Fearful Symmetry Diabetes Ther. 2021 Feb; 12(2): 461–464.Published online 2020 Dec 26. doi: 10.1007/s13300-020-00988-7
  4. Singh AK, Singh R. Hyperglycemia without diabetes and new-onset diabetes are both associated with poorer outcomes in COVID-19. Diabetes Res Clin Pract. 2020;167:108382. doi: 10.1016/j.diabres.2020.108382
  5. Reddy PK, Kuchay MS, Mehta Y, Mishra SK. Diabetic ketoacidosis precipitated by COVID-19: a report of two cases and review of literature. Diabetes Metab Syndr. 2020;14:1459–1462. doi: 10.1016/j.dsx.2020.07.050
  6. Maddaloni E, Buzzetti R. Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics. Diabetes Metab Res Rev. 2020 doi: 10.1002/dmrr.3321. 
  7. Prete M, Favoino E, Catacchio G, Racanelli V, Perosa F. SARS-CoV-2 inflammatory syndrome. Clinical features and rationale for immunological treatment. Int J Mol Sci. 2020;21:E3377. doi: 10.3390/ijms21093377. 
  8. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004;24:816–823. doi: 10.1161/01.ATV.0000122852.22604.78.



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