A Study to Identify Biomarkers of Hypoglycaemia in Patients With Type 2 Diabetes

NCT03102801 | Completed

• 1 other identifier: Version 2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Glucose is a sugar carried in the blood stream that body uses for energy. If someone has diabetes, blood glucose level can be erratic, sometimes becoming very low this is called Hypoglycaemia (or a "hypo"), and can happen when blood glucose levels drop below 4 mmol/l. So far in order to prove that a hypo happened for a patient, blood glucose level can only be measured at time of the hypo and not after it. In this study we are trying to identify certain chemical substances (biomarkers) in diabetic patients that may be measured in blood tests of the patient up to after 24 hours of the hypo and if we could prove that a hypo has happened we could adjust tablets and or insulin dosage in a way to prevent further hypos. The study will be conducted in the Diabetes Centre in Hull Royal Infirmary and will involve three visits to the diabetes centre. The study can finish in a week time after the first visit. Visit 1 is the screening visit to identify eligibility to take part in the study. Visit 2 insulin infusion will be given to make participants blood sugar level fall lower than normal for a short time and corrected quickly afterward. This is a stress for participant's body and should stimulate certain chemicals that we are trying to identify during hypo. In Visit 3, the main purpose of this visit which is done 24 hours after insulin infusion is to take a blood sample and check how participants is after visit 2. We will recruit 25 Type 2 Diabetic patients and 25 none diabetics to compare both results. Both groups should not have ischemic heart disease, underactive thyroid or seizures and on stable dosage of medications.

Conditions

Type 2 Diabetes Mellitus With Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Measurement of endothelial microparticles (composite number of CD105, CD106, CD142, CD54, CD62 & CD31) following hypoglycemic event

  6 months

Study Arms (2)

Type 2 diabetes arm

ACTIVE COMPARATOR

Both arms will be subjected to Hypoglycaemia and compare results

Drug: Humulin S

Non diabetics arm

ACTIVE COMPARATOR

Both arms will be subjected to Hypoglycaemia and compare results

Drug: Humulin S

Interventions

Humulin S DRUG

Humulin S used to induce hypoglycaemia

Non diabetics arm; Type 2 diabetes arm

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women who are white British or white Europeans between 40 - 70 years of age with type 2 diabetes.
• Duration of diabetes less than 10 years.
• Stable dose of medication over the last 3 months.
• No history of severe hypoglycemic in the preceding 3 months.
• No hypoglycemic unawareness
• Able to give informed consent.

You may not qualify if:

• Type 1 diabetes.
• Duration of diabetes of more than 10 years.
• Patients who are on insulin.
• HbA1c of ≥ 10%.
• BMI \<18 or \>50 kg/m2
• Alcohol excess defined as 14 units per week for a man or a woman. Binge drinking is defined 6 units for a man or women in a single drinking session.
• Renal impairment with estimated Glomerular Filtration Rate (eGFR\<60 ml/min/1.73 m2).
• Impaired Liver function tests defined as ALT or AST more than or equal 2.5 times upper limit of the normal.
• History or presence of malignant neoplasms within the last 5 years( except basal and squamous cell skin cancer and in-situ carcinoma).
• Psychiatric illness.
• Any form of gastrointestinal tract surgery.
• Any medications that can mask Hypoglycaemia such as B-Blockers or Clonidine.
• Medication that may cause change in glucose metabolism.
• Patients on any form of steroids in the last six months.
• Female who is pregnant, breast feeding or intended to become pregnant or of child bearing potential not using adequate contraceptive methods.

Sponsors & Collaborators

• University of Hull: lead

Study Sites (1)

Hull and east Yorkshire Hospitals NHS Trust

Hull, HU32RW, United Kingdom

Location

Related Publications (16)

• Moin ASM, Nandakumar M, Diboun I, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Hypoglycemia-induced changes in complement pathways in type 2 diabetes. Atheroscler Plus. 2021 Nov 18;46:35-45. doi: 10.1016/j.athplu.2021.11.002. eCollection 2021 Dec.

  PMID: 36643727 DERIVED

• Ramanjaneya M, Bettahi I, Pawar K, Halabi NM, Moin ASM, Sathyapalan T, Abou-Samra AB, Atkin SL, Butler AE. MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes. Int J Mol Sci. 2022 Nov 24;23(23):14696. doi: 10.3390/ijms232314696.

  PMID: 36499023 DERIVED

• Moin ASM, Sathyapalan T, Atkin SL, Butler AE. The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians. Cardiovasc Diabetol. 2022 Oct 6;21(1):202. doi: 10.1186/s12933-022-01639-w.

  PMID: 36203210 DERIVED

• Ramanjaneya M, Priyanka R, Bensila M, Jerobin J, Pawar K, Sathyapalan T, Abou-Samra AB, Halabi NM, Moin ASM, Atkin SL, Butler AE. MiRNA and associated inflammatory changes from baseline to hypoglycemia in type 2 diabetes. Front Endocrinol (Lausanne). 2022 Aug 9;13:917041. doi: 10.3389/fendo.2022.917041. eCollection 2022.

  PMID: 36017315 DERIVED

• Nandakumar M, Moin ASM, Ramanjaneya M, Qaissi AA, Sathyapalan T, Atkin SL, Butler AE. Severe iatrogenic hypoglycaemia modulates the fibroblast growth factor protein response. Diabetes Obes Metab. 2022 Aug;24(8):1483-1497. doi: 10.1111/dom.14716. Epub 2022 May 3.

  PMID: 35415885 DERIVED

• Moin ASM, Nandakumar M, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes. Front Mol Biosci. 2021 Dec 1;8:744459. doi: 10.3389/fmolb.2021.744459. eCollection 2021.

  PMID: 34926573 DERIVED

• Butler AE, Al-Qaissi A, Sathyapalan T, Atkin SL. Angiopoietin-1: an early biomarker of diabetic nephropathy? J Transl Med. 2021 Oct 13;19(1):427. doi: 10.1186/s12967-021-03105-9. No abstract available.

  PMID: 34645474 DERIVED

• Atkin AS, Moin ASM, Nandakumar M, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Impact of severe hypoglycemia on the heat shock and related protein response. Sci Rep. 2021 Aug 23;11(1):17057. doi: 10.1038/s41598-021-96642-8.

  PMID: 34426634 DERIVED

• Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection? Front Endocrinol (Lausanne). 2021 Jun 23;12:665134. doi: 10.3389/fendo.2021.665134. eCollection 2021.

  PMID: 34248841 DERIVED

• Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity. Front Endocrinol (Lausanne). 2021 Jun 25;12:658304. doi: 10.3389/fendo.2021.658304. eCollection 2021.

  PMID: 34248840 DERIVED

• Moin ASM, Kahal H, Al-Qaissi A, Kumar N, Sathyapalan T, Atkin SL, Butler AE. Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia. BMJ Open Diabetes Res Care. 2021 Apr;9(1):e002211. doi: 10.1136/bmjdrc-2021-002211.

  PMID: 33931404 DERIVED

• Atkin AS, Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Plasma heat shock protein response to euglycemia in type 2 diabetes. BMJ Open Diabetes Res Care. 2021 Apr;9(1):e002057. doi: 10.1136/bmjdrc-2020-002057.

  PMID: 33879515 DERIVED

• Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes. Front Endocrinol (Lausanne). 2021 Mar 30;12:651009. doi: 10.3389/fendo.2021.651009. eCollection 2021.

  PMID: 33859620 DERIVED

• Moin ASM, Sathyapalan T, Diboun I, Atkin SL, Butler AE. Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19. Sci Rep. 2021 Mar 19;11(1):6428. doi: 10.1038/s41598-021-85760-y.

  PMID: 33742062 DERIVED

• Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Do biomarkers of COVID-19 severity simply reflect a stress response in type 2 diabetes: Biomarker response to hypoglycemia. Metabolism. 2021 Jan;114:154417. doi: 10.1016/j.metabol.2020.154417. Epub 2020 Nov 4. No abstract available.

  PMID: 33157081 DERIVED

• Moin ASM, Sathyapalan T, Atkin SL, Butler AE. Pro-fibrotic M2 macrophage markers may increase the risk for COVID19 in type 2 diabetes with obesity. Metabolism. 2020 Nov;112:154374. doi: 10.1016/j.metabol.2020.154374. Epub 2020 Sep 16. No abstract available.

  PMID: 32949593 DERIVED

MeSH Terms

Interventions

Insulin, Regular, Human

Intervention Hierarchy (Ancestors)

Insulin; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: April 6, 2017
• Study Start: March 1, 2017
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: November 1, 2018

Record last verified: 2018-10

Locations

GB (1)